Dendritic TADDOLs: Synthesis, characterization and use in the catalytic enantioselective addition of Et2Zn to benzaldehyde

Article abstract of DOI:10.1002/(SICI)1521-3765(19991105)5:11<3221::AID-CHEM3221>3.0.CO;2-P

The versatile chiral ligand for polar metal centers, TADDOL ((R,R)-a,a,a′,a′-tetraaryl-1,3-dioxolane-4,5-dimethanol), has been incorporated as core building block into dendrimers by way of benzylation of a fourfold phenolic derivative (hexol 2) with Frech

Full text of DOI:10.1002/(SICI)1521-3765(19991105)5:11<3221::AID-CHEM3221>3.0.CO;2-P

FULL PAPER
Dendritic TADDOLs: Synthesis, Characterization and Use in the Catalytic
Enantioselective Addition of Et2Zn to Benzaldehyde
P. Beat Rheiner and Dieter Seebach*[a]
Abstract: The versatile chiral ligand for
polar metal centers, TADDOL ((R,R)-
a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-di-
methanol), has been incorporated as
core building block into dendrimers by
way of benzylation of a fourfold phe-
cal activity measurements; one of the
branch precursors with four octyl groups
crystallized in an intriguing packing
pattern. From the spectra and from the
specific and molar optical rotations,
there was no indication for the forma-
tion of chiral secondary structures of up
to the third generation. The new TAD-
reaction rates observed with the novel
catalysts were compared with those of
the simple Ti TADDOLate: up to the
second generation there was no detect-
able decrease of selectivity (ˆ98:2), and
the rates hardly decreased up to the
third generation; also, enantiomeric
branches caused no change of stereo-
selectivity within experimental error.
Thus, there may be applications for the
special properties (such as high molec-
ular weight, good solubility, spacing of
central site from cross-linked polymer
matrix) of dendritically modified chiral
catalyst ligands.
Â
nolic derivative (hexol 2) with Frechet-
type branches of up to fourth genera-
tion. These carry either benzyl (3 ± 7) or
octyl groups (33 ± 35) at the periphery, or
they contain chiral branching units (18 ±
20, 36), derived from (R)- or (S)-3-
hydroxybutanoic acid. The dendritic
compounds of molecular weight up to
13626 have been fully characterized,
including by MALDI-TOF mass spec-
trometry, NMR spectroscopy, and opti-
DOLs
were
converted
to
Ti
TADDOLates, which were employed
as catalysts for the addition of Et2Zn to
PhCHO. The stereoselectivities and the
Keywords: alkylations ´ asymmetric
catalysis ´ catalysts ´ dendrimers ´
TADDOLs
interact with each other or with the dendritic branches,[2, 7]
and it is advisable to use inert apolar dendritic branches
around the (polar, functionalized) catalytically active site(s).[9]
Finally, it is not to be expected that remote chiral units in a
dendrimer have a strong influence on the stereoselectivity
with which a catalytic site performs.[10]
In view of possible applications of derivatives of TADDOL
((R,R)-a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-dimethanol, Fig-
ure 1)[11] in membrane reactors and in dendritically cross-
linked polymer particles,[12] we have now prepared com-
pounds with the propeller-type[13] TADDOL moiety in the
center[14] carrying four dendritic arms. These, in turn, were of
Introduction
A variety of chiral dendritic catalysts has been described.[1] In
most cases, chiral, catalytically active units have been attached
as end groups to the periphery of achiral dendrimers,[2±4]
providing high molecular weight catalysts which should be
easily removed from a reaction mixture.[5] A second type of
chiral dendritic catalysts employs chiral branches, which are
attached to an achiral catalytically active core unit,[6] an
approach which has, so far, not been very successful.
It is known that only dendrimers of lower generations
(below the critical mass) can be suitable carriers for catalyti-
cally active sites: if the catalytic sites are at the periphery of
high-generation dendrimers (with a densely packed surface)
they interfere with each other; this may result in decreased
selectivity.[7] If the catalytic site is located inside a high-
generation dendrimer, the branches prevent access of sub-
strates.[8] Furthermore, catalytically active sites must not
Â
three different types: ¹classicalª achiral Frechet dendrimer
[a] Prof. Dr. D. Seebach, Dr. P. B. Rheiner
Laboratorium für Organische Chemie
der Eidgenössischen Technischen Hochschule
ETH Zentrum, Universitätstrasse 16
CH-8092 Zürich (Switzerland)
Figure 1. Formula of TADDOL[11] and overlay of 19 X-ray structures of
various C1- and C2-symmetrical TADDOL derivatives.[13]
Fax: (‡41)1-632-1144
E-mail: seebach@org.chem.ethz.ch
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D. Seebach and P. B. Rheiner
FULL PAPER
branches,[15] arms with chiral
branching units (derived from
3-hydroxybutanoic
and branches with peripheral
octyl groups (mimicking mi-
celles,[17±19] increasing the mo-
lecular weight and the solubility
in hydrocarbons). The synthesis
and characterization of these
compounds, as well as their
use as ligands in titanates for
OTBDMS
MgBr
TBDMSO
HO
OH
OTBDMS
acid[16]),
O
O
TBAF
O
O
O
O
O
O
OH
OH
OH
OH
OMe
OMe
THF
THF
(79%)
(87%)
TBDMSO
OTBDMS
HO
OH
1
2
Scheme 1. Synthesis of the TADDOL core building block 2 from (R,R)-tartrate acetonide.
the enantioselective catalysis of Et2Zn addition to benzalde-
hyde[20] (as a test reaction) are subject of the present paper.
the attachment of dendritic branches. The relatively large
distance between the coupling sites should also allow for
coupling with sterically demanding branches. The synthesis of
the TADDOL core started from the acetal of (R,R)-dimethyl
tartrate,[21] to which was added an excess of the Grignard
reagent prepared from 4-tert-butyldimethylsilyloxyphenyl
bromide. The resulting TADDOL derivative 1 was isolated
by crystallization as a 1:1 complex with methanol. Cleavage of
the four protecting groups with Bu4NF gave the hexol 2 in
good yield (Scheme 1).
Results and Discussion
Preparation of the hexol 2 for the TADDOL core units: For
the preparation of the new dendritic derivatives, the para
positions of the four phenyl groups in TADDOL, which point
away from the metal-bonding site, were considered ideal for
Figure 2. Formulae of TADDOL dendrimers 3 ± 5 of 0th, first, and second generation. MALDI-TOF spectra of dendrimers 4 and 5, demonstrating the
monodispersity of the compounds.
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Dendritic TADDOLs
3221±3236
Figure 3. Formulae and MALDI-TOF spectra of TADDOL dendrimers 6 and 7 of third and fourth generation. The signals besides the molecule peaks might
stem from molecules which are produced during evaporation and ionization of the molecules from the matrix (ªin-source decayº[22]).
Synthesis and characterization of dendrimers with a TAD-
first to fourth generation were carried out in acetone (508C/
K2CO3). Dendrimers 3 ± 7 were all purified by column
chromatography and were isolated in yields of up to 87%.
DOL core and achiral branches: For the first series of
[15]
Â
dendrimers, Frechetꢁs achiral poly(benzyl ether) branches,
1
up to the fourth generation, were used. For the coupling of the
branches with the core hexol 2, reaction conditions were
similar to those for the branch syntheses; etherification of 2
with benzylic bromide gave ¹dendrimerª 3 of 0th generation
(DMF/K2CO3); the coupling reactions of the dendritic branch
bromides with the TADDOL unit to give dendrimers 4 ± 7 of
They have been fully characterized by H and 13C NMR and
IR spectroscopy, MALDI-TOF MS, and elemental analysis
(Figures 2, 3).
Besides the major products (dendrimers 4 ± 6), C1-sym-
metrical minor products (10 ± 20%) were formed (higher Rf
1
value). It follows from H NMR and MALDI-TOF spectra
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D. Seebach and P. B. Rheiner
FULL PAPER
Figure 4. Formula and MALDI-TOF spectrum of the impurity in the desired dendrimer 5, formed by fivefold coupling of the hexol 2 with the corresponding
benzylic branch bromide.
that these are TADDOLs with
five branches; see Figure 4 for
an example. It is surprising that
a tertiary OH group of the
TADDOL 2 competes success-
fully with the four phenolic OH
groups in these etherifications.
1
Figure 5 shows the H NMR
spectrum of third-generation
dendrimer 6. Specific signals
from branch and core hydro-
gens can be recognized: the
TADDOL unit at d ˆ 1.0
(2 CH3 groups, H), 4.15 (2
tertiary OH groups, G, identi-
fied by H/D exchange) and at
4.4 (2 CH groups, F); two dou-
blets (D, E) each from the two
diastereotopic para-substituted
benzene rings. A set of signals
at d ˆ 6.5 (A, B, C) belongs to
the aromatic hydrogens be-
tween the oxygens in the
branches; the three signals be-
long to the three generations,
and they appear at higher fields
as we approach the core unit.
For the characterization of
chiral dendrimers, optical rota-
tion values are relevant,[1] be-
cause they may indicate con-
formational changes which oc-
cur in the dendritic structures.
Normally, the (molar) optical
rotation value of each chiral
Figure 5. 1H NMR spectrum (500 MHz) of third-generation dendrimer 6. The individual hydrogens and the
signals assigned to them are labelled A ± H.
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Dendritic TADDOLs
3221±3236
building block in a dendrimer is constant,[23, 24] and the
corresponding contributions of different chiral building
blocks can be added up to give the value for the whole
molecule.[16, 24] Only serious steric hindrance or interaction
with other building blocks (e.g. H bonds in peptide structures)
can lead to exceptions to this rule. The dendrimers 3 ± 7 of 0th
to fourth generation, which contain only one chiral unit in the
center, were thus expected to show a decreasing specific
rotation value [a]D with increasing molecular weight, but a
constant molar rotation value [f]D. This is in fact the case, as
can be seen from Table 1.
Table 2. Comparison of the selectivity of the TADDOL dendrimers 3 ± 7
when employed as ligands on titanium for catalysis of the enantioselective
addition of Et2Zn to PhCHO. Although the difference is not dramatic,
there is clearly a sudden decrease (from above 98 to below 96% of S
enantiomer) from TADDOL and the lower generation dendrimers 3 ± 5, on
the one hand, to the higher generation dendrimers 6 and 7, on the other
hand.
O
OH
0.2 equiv Ti TADDOLate
+
1.8 equiv Et2Zn
H
(S)
1.2 equiv Ti(OiPr)4
toluene, -20°C
major enantiomer
PhCHO Cat*
Conc
Conversion S/R
[%][c]
1
[b]
[mmol] [mg][a] [mmolmL
]
TADDOL
5.0
447
178
348
688
1367
545
0.25
0.25
0.25
0.25
0.25
0.13
quant.
98.7
96.8
96.5
94.4
46.8
99:1
98.5:1.5
98:2
98:2
95.5:4.5
94.5:5.5
dendrimer G0 3 1.0
dendrimer G1 4 1.0
dendrimer G2 5 1.0
dendrimer G3 6 1.0
dendrimer G4 7 0.2
Table 1. Comparison of the specific ([a]) and molar ([f]) optical rotations
of TADDOL dendrimers 3 ± 7.
Mr
[a]RDT
[f]RDT
dendrimer G0 3
dendrimer G1 4
dendrimer G2 5
dendrimer G3 6
dendrimer G4 7
891
1740
3438
6834
13626
49.24
439
462
455
437
458
26.55
13.23
6.40
[a] Amount of free auxiliary before loading with titanate. [b] Concentra-
tion in mmol PhCHO per mL toluene. [c] After 2 h reaction time.
3.36
when we go from the third- (6) to the fourth-generation (7)
derivatives.[25]
Catalysis with the Ti complexes of dendrimers 3 ± 7 containing
achiral branches: To measure the influence of the dendritic
branches on the catalytic activity and stereoselectivity of the
TADDOL, we tested dendrimers 3 ± 7 in the enantioselective
addition of Et2Zn to PhCHO. In order for a comparison of the
results with those obtained for the TADDOL to be possible,
20 mol% of the high molecular weight dendritic catalyst had
to be employed. The titanium complex of the simple
TADDOL catalyzes the reaction with very high enantiose-
lectivity (S:R 99:1[20]). Table 2 shows that there is a decrease
of enantioselectivity with increasing generation number of the
dendritic catalyst. While the dendrimers 3 ± 5 (up to the
second generation) catalyze the reaction with almost the same
selectivity as the simple TADDOL, there is a clear-cut
decrease from the second to the third generation.
We have also compared the reaction rates (Figure 6) to find
that even though all dendritic TADDOLs catalyze the
addition at a similarly high rate, the reactions become steadily
slower with the generation number. The reactions with the Ti
complexes of the dendrimers 3 ± 6 were run under the same
conditions, while a smaller amount of PhCHO and Et2Zn and
also a lower concentration of the substrate were used for the
catalysis with fourth-generation dendrimer 7 (so that the
curve for 7 in Figure 6 is not really comparable).
Both the rate and the stereoselectivity of the addition of
Et2Zn to PhCHO catalyzed by Ti TADDOLate are hardly
changed when the catalyst is replaced by dendritic analogues
3 ± 5 (up to second-generation). The performance decreases
Figure 6. Comparison of the reaction rates of the Et2Zn addition to
PhCHO catalyzed by TADDOL and the dendritic TADDOL derivatives
3 ± 7. Higher dilution was used with the dendritic ligand 7 (see accompany-
ing text and experimental section).
Synthesis and characterization of dendrimers with a TAD-
DOL core and chiral branches. We next investigated whether
additional stereogenic centers in the dendritic branches would
influence the selectivity of the catalyzed reaction. In our
previous work on chiral dendrimers, we reported the synthesis
of doubly[16] and triply[26] branching chiral building blocks,
which are obtained in a few steps from 3-hydroxybutanoic
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D. Seebach and P. B. Rheiner
FULL PAPER
acid, both enantiomers of which
are readily available: the R enan-
tiomer by depolymerization of the
commercial biopolymer PHB,[27]
the S enantiomer by yeast reduc-
tion of b-keto esters,[28] either one
of the two by Noyori hydrogena-
tion.[29] From hydroxybutanoic acid
the dioxanones 8 and ent-8 were
prepared[16] and stereoselectively
alkylated with bromide 9 to give
derivatives 10 and ent-10, reduction
of which furnished the chiral diols
11 and ent-11 (Scheme 2), and
these, in turn, were converted to
the chiral branch units 12 ± 17 of
the first and second generation
(Scheme 3).
OTBDPS
9
1) (CH3)3CCHO
Dowex 50W
CH2Cl2, ∆
OH
O
O
H
NaBH4
Br
OH
OH
O
O
O
O
OH
THF/MeOH
2) Recryst.
Et2O/pentane
LDA, THF
-78°C
O
OTBDPS
(55%)
(90%)
(86%)
OTBDPS
8
10
11
OTBDPS
9
1) (CH3)3CCHO
Dowex 50W
CH2Cl2, ∆
OH
O
O
H
Br
NaBH4
OH
OH
O
O
O
O
OH
THF/MeOH
2) Recryst.
Et2O/pentane
LDA, THF
-78°C
O
OTBDPS
(48%)
(71%)
(91%)
OTBDPS
ent-8
ent-10
ent-11
Coupling of the chiral benzylic
branch bromides 14 of first and 17
of second generation with the
TADDOL core 2 was achieved as
for the achiral branches (acetone/
K2CO3). First-generation dendrim-
er 18 (Figure 7) and the two dia-
Scheme 2. Preparation of the enantiomerically pure diols 11 and ent-11 from the corresponding (R)- and (S)-3-
hydroxybutanoic acids.
O
O
R
Br
12 R = OTBDPS
13 R = OH
14 R = Br
a)
O
O
OH
O
b)
(95%)
(83%)
NaH/THF
NaH/THF
OH
O
O
O
O
OTBDPS
O
O
O
O
OH
OH
11
O
O
O
O
O
O
O
O
O
O
R
O
Br
15 R = OTBDPS
16 R = OH
17 R = Br
a)
b)
18
C135H142O16
Mr : 2020.56
O
O
O
O
Figure 7. Formula of first-generation den-
OH
drimer 18 with chiral branches.
OH
Br
O
O
O
NaH/THF
(86%)
stereomeric dendrimers 19 and 20
were thus obtained in yields of up
to 80%. Figure 8 shows the formu-
lae and MALDI-TOF mass spectra
of 19 and 20. Again, the dendrimers
were purified by column chroma-
tography and fully characterized.[30]
Due to the chiral branching units,
OTBDPS
O
ent-11
R
ent-15 R = OTBDPS
ent-16 R = OH
ent-17 R = Br
a)
b)
Scheme 3. Preparation of the chiral branches of first and second generation from the diols 11 and ent-11.
Conditions: a) TBAF, THF (84 ± 89%); b) CBr4, PPh3, THF (43 ± 47%).
1
the H NMR spectra of the den-
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Dendritic TADDOLs
3221±3236
drimers 19 and 20 are more
complex, but also easier to
interpret. In the 1H NMR spec-
trum of second-generation den-
drimer 19 (Figure 9), the typical
TADDOL signals (A, B, H, O)
can again be easily recognized.
In addition, the signals of the
protons close to the stereogenic
centers in the branches (F, J ±
N) all display unique shifts.
The comparison of the opti-
cal rotation values of these
dendrimers is especially inter-
esting, because, according to
the rule mentioned above, the
contributions to the molar opti-
cal rotation values by the build-
ing blocks should add up to the
molar optical rotation value of
the entire dendrimer (in the
absence of contributing chiral
conformations). Since the val-
ues of the branches of opposite
configuration are of opposite
sign, the molar optical rotation
value of the dendrimers with
achiral branches (such as 5)
should lie in the middle of the
values for dendrimers 19 and
20. The numbers in Table 3
show that these expectations
are met when we use a [f]D
contribution of ca. 20 from each
chiral branching unit (the alco-
hol 16 has a [f]D of 28). We
should keep in mind that in the
case of the dendrimers 19 and
20, a difference of Æ1 in the
measured specific rotation
leads to a difference of Æ37 in
the molar rotation value.
Figure 8. Formulae and MALDI-TOF mass spectra of the diastereomeric second-generation dendrimers 19 and
20.
branches, the enantioselective addition of Et2Zn to PhCHO
was used as a test. It was especially interesting and informa-
tive to see whether the two (R,R)-TADDOL units in 19 and 20
with enantiomeric branch units would give different results. It
was found that neither of the two enantiomeric branches of
the dendrimers influenced the selectivity of the reaction
significantly (Table 4).
Also, the titanates of the second-generation dendrimer 5
and of TADDOLs 19 and 20 all catalyzed the reaction at
almost exactly the same rate. Obviously, the distance of
thirteen bonds from the nearest stereogenic center of the
branches to the tertiary OH group of the TADDOL unit is too
large to influence the stereochemical outcome of the cata-
lyzed reaction.
Table 3. Comparison of the specific ([a]) and molar ([f]) optical rotations
of the TADDOL dendrimers 18 ± 20 with chiral branches. To test the
addition rule (see accompanying text) the values for the chiral branch unit
16 and for the dendrimer 5 with achiral branches are also included.
Mr
[a]
[f]
dendrimer G1* 18[a]
2021
3719
3719
3438
815
29.10
588
dendrimer G1F ± G1*(A) 19[a]
dendrimer G1F ± G1*(B) 20[a]
dendrimer G2F 5[a]
14.43
10.85
13.23
3.50
537
404
455
28
branch alcohol 16[a]
[a] * ˆ chiral; (A) and (B) represent the two enantiomeric diols, F ˆ po-
Â
ly(benzyl ether) branches after Frechet et al.
Catalysis with the titanium complexes of dendrimers 19 and
20 containing enantiomeric chiral branches: To compare the
catalytic activity of the dendrimers with and without chiral
In summary we have found that, under the conditions
applied, dendritic branches of up to the second generation,
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D. Seebach and P. B. Rheiner
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Using the same strategy, we
have now attached alkyl chains
at the periphery of dendritic
TADDOLs, making the TAD-
DOL unit soluble for catalysis
in apolar solvents such as hex-
ane.
Achiral branches were again
synthesized following the meth-
[15]
Â
od of Frechet et al.: starting
from octyl bromide and the
branching unit 3,5-dihydroxy
methyl benzoate, the achiral
branches 21 ± 23 (first genera-
tion) and 24 ± 26 (second gen-
eration) were prepared (Fig-
ure 10). Compared with those
for the branches carrying ben-
zylic end groups, the coupling
yields were lower and the puri-
fication of the oily products by
column chromatography was
more difficult.
To our surprise, single crys-
tals of the second-generation
alcohol 25 were obtained by
crystallization from CH2Cl2;
these were analyzed by X-ray
diffraction. Like lipids in mem-
branes, the octyl chains pack in
the crystalline state in a highly
regular manner. The molecules
seem to be held together mainly
by hydrophobic interactions
rather than by H bonds: there
are crystal structures that con-
tain C H ´´´ O distances of up
to 3.5 Š,[31] which is clearly
shorter than the closest neigh-
bourhoods of any carbon and
oxygen atoms, as outlined in
Figure 11a (an average O H ´´´
O hydrogen bond is ca. 2.4 Š
long[32]). In the crystal packing
the alcohol 25 forms layers as
shown in Figure 11b.[33]
Figure 9. 1H NMR spectrum (500 MHz) of second-generation dendrimer 19. The signals are well separated, so
that more hydrogens (A ± O) can be assigned than for the dendrimer 6 (having no chiral branching units).
Table 4. Comparison of the selectivities of TADDOL dendrimers 5 (with achiral branching units) and 19 and 20
(with chiral branching units) when employed as ligands on titanium in the catalytic enantioselective Et2Zn
addition to PhCHO.
O
OH
Ti TADDOLate
+
1.8 equiv Et2Zn
H
(S)
1.2 equiv Ti(OiPr)4
toluene, -20°C
major enantiomer
Cat*
[mol%]
PhCHO
[mmol]
Cat*
[mg][a]
Conc
[mmolmL ]
Conversion
[%][c]
S/R
1
[b]
monomeric TADDOL
20
20
20
20
5
447
521
521
688
0.25
0.18
0.18
0.18
quant.
n.d.
93.8
98:2
98:2
98.5:1.5
98:2
dendrimer G1F ± G1*(A) 19[d]
dendrimer G1F ± G1*(B) 20[d]
dendrimer G2F 5[d]
0.7
0.7
0.7
96.5
[a] Amount of free auxiliary before loading with titanate. [b] Concentration in mmol PhCHO per mL toluene.
[c] After 2 h reaction time. [d] The abbreviations are as in Table 3.
regardless of whether they contain additional stereogenic
centers, do not really influence the catalytic performance of
the dendritic Ti TADDOLates compared to the simple Ti
TADDOLate.
O
O
O
O
R
O
O
O
O
Synthesis and characterization of dendrimers with a TAD-
DOL core and octyl end groupsÐmodel for an inverse
R = COOMe
R = CH2OH
R = CH2Br
21
22
23
R
micelle: In 1985 dendrimers were described as ªunimolecular
R = COOMe
R = CH2OH
R = CH2Br
24
[17]
micellesº
because of their spherical shape and their large
25
26
number of aliphatic end groups, which can determine the
solubility of the entire molecule. Meijer et al. were the first to
describe dendrimers using the model of an inverse micelle.[18]
Figure 10. Achiral dendritic branches 21 ± 26 bearing octyl groups at the
periphery.
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Chem. Eur. J. 1999, 5, No. 11

Dendritic TADDOLs
3221±3236
dendrimers 33 ± 36 were isolated as oils which were difficult to
purify; only small amounts of these hexane- and pentane-
soluble compounds were synthesized, so that no further
experiments have, as yet, been carried out with them.
Conclusion
We have shown that dendritic branches attached to a
conformationally rigid chiral catalyst moiety, such as the
TADDOLate, influence the performance only when the
branches become sterically too demanding and access of
substrates is therefore hindered. For the TADDOL ligand, we
Â
have defined the limiting generation size 2 of Frechet
branches, four of which may be attached without influencing
the activity of a catalytic titanium center; we have also shown
that additional chiral building blocks in the dendritic structure
may not interfere at all with the performance of a TADDO-
Late site, if placed far enough away from the catalytic center.
This knowledge is most important in view of possible
applications involving this kind of catalyst. Of course, a
dendritically modified catalyst is only of interest if there are
advantages, such as the large molecular weight (cf. membrane
reactor), better solubility (cf. inverse or unimolecular mi-
celle), simpler recovery and separation from products, or
better performance when incorporated in polymers.[12] Ex-
periments along these lines are currently being performed in
our laboratory.
Figure 11. ORTEP plots from the crystal structure of compound 25
showing: a) two molecules and the distances between the atoms which
could form weak H bonds, and b) a plane out of the crystal lattice with a
highly regular pattern of molecules held together by hydrophobic
interaction.
Experimental Section
For more details see P. B. Rheiner, Dissertation No. 12773, ETH Zürich,
1998.
General: Starting materials and reagents: (R,R)-dimethyl tartrate (Chemi-
sche Fabrik, Uetikon) and Et2Zn (Schering, Bergkamen) were used as
received without further purification. A 2m stock solution of Et2Zn was
prepared from Et2Zn (20.5 mL) and toluene (79.5 mL). (iPrO)4Ti (Hüls,
Troisdorf) and PhCHO were distilled. The solvents used in the reactions
were of p.a. quality or purified and dried according to standard methods.
All other chemicals were used as commercially available.
Besides the achiral branch precursors 21 ± 26, we have also
prepared the chiral branch derivatives 27 ± 29 of the second
and 30 ± 32 of the third generation (Figure 12); while the
coupling of chiral diol 11 with first-generation bromide 23 was
almost quantitative, the same reaction with the second-
generation bromide 26 gave
Equipment: TLC: precoated silica gel 25 Durasil UV254 plates (Macherey-
Nagel); visualization by UV254 light, development using phosphomolybdic
much poorer yields. The subse-
quent deprotection and bromi-
nation steps gave consistent
yields of over 80%. The achiral
O
O
branches were coupled with the
core hexol 2 under the usual
O
O
O
O
O
O
conditions to give dendrimers
33 ± 35 of 0th, first, and second
generation (Figure 13), and the
chiral-branch bromide 32 was
used for the preparation of the
third-generation dendrimer 36
(Figure 14). The latter com-
pound contains 32 peripheral
octyl groups (ªinverse mi-
celleº[18]). The coupling yields
were mostly moderate, and the
O
O
O
O
O
O
O
O
O
O
R
R
O
O
R = OTBDPS
R = OH
R = OTBDPS
R = OH
27
28
29
30
31
32
R = Br
R = Br
Figure 12. Chiral first- and second-generation branches 27 ± 32 with octyl groups at the periphery obtained by
benzylation of the diol 11 with the halides 23 and 26, respectively.
Chem. Eur. J. 1999, 5, No. 11
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D. Seebach and P. B. Rheiner
FULL PAPER
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
OH
OH
OH
OH
OH
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
33
C63H94O8
Mr : 979.42
34
C123H182O16
Mr : 1916.75
35
C243H358O32
Mr : 3791.42
Figure 13. TADDOL dendrimers 33 ± 35 of 0th to second generation with achiral branches bearing octyl chains on the periphery.
CDCl3 solutions (unless stated otherwise). IR: CHCl3 solutions; Perkin ±
Elmer FT-IR 1600 (s ˆ strong, m ˆ medium, w ˆ weak). MS: Hitachi ±
Perkin ± Elmer RMU-6M (EI), VG ZAB2-SEQ (FAB); MALDI-TOF
spectra: Bruker Reflexꢂ Spectrometer (N2 laser, 337 nm), matrices: a-
cyano-4-hydroxycinnamic acid (CCA), 2,5-dihydroxybenzoic acid (2,5-
DHB), 2-(4-hydroxyphenylazo)benzoic acid (HABA), 2,4,6-trihydroxya-
cetophenone (THA), fragment ions in m/z with relative intensities (%) in
parentheses. Elemental analyses were performed by the Microanalytical
Laboratory of the Laboratorium für Organische Chemie (ETH Zürich).
Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication no. CCDC-116051.
Copies of the data can be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax: (‡44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk). Nomenclature of dendrimers and den-
dritic branches is used according to our published convention.[34]
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
OH
O
O
O
O
O
O
O
O
O
O
O
O
Cleavage of the alcohol protecting groups TBDMS and TBDPS
O
O
O
O
O
O
General procedure I (GP I): A solution of the protected alcohol (1 equiv)
in THF was cooled to ice-bath temperature. After addition of 1 ± 2 equiv of
tetrabutylammonium fluoride (TBAF) for each protecting group the
reaction mixture was stirred for at least 20 h (TLC control). To work the
reaction up, H2O was added under ice-bath cooling and the aqueous layer
was extracted (3 Â Et2O, 3 Â CH2Cl2). The combined organic layers were
dried over MgSO4 and the solvents were removed under vacuum.
O
O
O
O
O
O
O
O
O
O
36
Coupling of benzylic branch bromides to the TADDOL core
C503H750O64
Mr : 7821.30
General procedure II (GP II): To a solution of TADDOL in acetone were
added bromide (4 equiv) in acetone and K2CO3 (4 equiv), and the reaction
mixture was stirred at ca. 508C for about 60 h (TLC monitoring). After
being cooled to RT, the salt was filtered off and most of the acetone was
evaporated under vacuum. The remaining solution was diluted with CH2Cl2
and washed with H2O. The organic layer was washed again with H2O and
the combined aqueous layers were extracted (2 Â CH2Cl2). The combined
organic layers were dried over MgSO4 and the solvent evaporated under
vacuum. The crude product can be purified by flash column chromatog-
raphy (20 weight equiv SiO2, CH2Cl2). All by-products are eluted faster
than the desired product, which can be obtained from the column by adding
a few drops of acetone to the solvent.
Figure 14. Formula of third-generation dendrimer 36 with chiral branches
and octyl groups at the periphery (cf. the term unimolecular micelle[17]).
acid solution (phosphomolybdic acid (25 g), Ce(SO4)2 ´ 4H2O (10 g), H2SO4
(60 mL), H2O (940 mL)). Flash column chromatography (FC): SiO2 60
(0.040 ± 0.063 mm, Fluka), pressure 0.2 ± 0.6 bar. M.p.: open glass capilla-
ries, Büchi 510 (Tottoli apparatus), 508C range Anschütz thermometers,
uncorrected. [a]D at RT (ca. 208C) Perkin ± Elmer 241 polarimeter (p.a.
solvents, Fluka). Capillary gas chromatography (GC): Carlo Erba Fracto-
vap 4160 with Carlo Erba DP 700 CE integrator or Hewlett Packard 5890
Series II with HP 6890 Series Injector; column: FS-Hydrodex b-PM
(50 m  0.25 mm) (Macherey ± Nagel); injector temp. 2208C, detector
temp. 2208C (FID), heating rate: 808, 18min 1; pressure: 1.3 bar H2. 1H
and 13C NMR spectra: Bruker AMX-300, AMX-400, AMX-II-500, Varian-
XL-300, Gemini-200 or Gemini-300; d downfield of TMS (d ˆ 0), J in Hz;
Coupling of benzylic branch bromides to the chiral building blocks
General procedure III (GP III): THF was added to NaH (6 equiv) and the
mixture was cooled to ice-bath temperature. After addition of a solution of
the chiral diol in THF, the suspension was stirred for 1.5 h at RT. A solution
of the benzylic bromide (2.5 equiv) in THF was added slowly and the
3230
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Dendritic TADDOLs
3221±3236
reaction mixture was stirred for 3 h at RT and then heated under reflux for
15 h. After cooling of the mixture to ice-bath temperature, H2O was added
and the layers were separated. The aqueous layer was extracted (3 Â Et2O),
saturated with NaCl, and extracted again with CH2Cl2. The combined
organic layers were dried over MgSO4 and the solvents were evaporated
under vacuum.
2 CH3), 4.00 (s, 2H, 2 OH), 4.48 (s, 2H, 2 CH), 5.01 (s, 4H, 2 CH2(P)), 5.06
(s, 4H, 2 CH2(P)), 6.84 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 6.93 (d, J ˆ 9.0, 4H, 4
arom. H(c)), 7.22 ± 7.47 (m, 28H, 8 arom. H(c), 20 arom. H(P)); 13C NMR
(125 MHz): d ˆ 27.2, 69.9, 70.0, 77.6, 81.1, 109.2, 113.5, 114.3, 127.4, 127.6,
127.9, 128.0, 128.6, 128.9, 129.7, 135.3, 137.0, 138.6, 157.9, 158.0; IR (CHCl3):
nÄ ˆ 3357w, 3008w, 1671w, 1608m, 1582w, 1509s, 1454w, 1380w, 1295w,
1081w, 1055w, 1026m, 885w, 834w cm 1; MALDI-TOF MS (CCA): m/z:
Bromination of the benzylic branch alcohols
‡
914.3 ([M‡Na] ); C59H54O8 (891.07): calcd C 79.53, H 6.11; found C 79.51,
General procedure IV (GP IV): PPh3 (1.5 equiv) and CBr4 (1.5 equiv) were
added in this order to a solution of benzylic alcohol (1 equiv), which was
cooled in an ice bath, and the reaction mixture was stirred for 45 min at
08C. Aluminum foil was then wrapped around the flask to prevent
exposure to light and the mixture was stirred for an additional 20 h at RT to
give a milky white suspension. After addition of H2O, the layers were
separated; the aqueous layer was saturated with NaCl and extracted (2 Â
CH2Cl2). The combined organic layers were dried over MgSO4 and the
solvents were evaporated under vacuum.
H 6.01.
(Bn)8 {[G1]F}4 [Phe-TADDOL] (4): As described in GP II, a solution of
[15]
Â
first-generation Frechet-type branch bromide (3.07 g, 8 mmol) in ace-
tone (10 mL) was added to a solution of TADDOL 2 (1.06 g, 2 mmol) in
acetone (50 mL). To this solution was added K2CO3 (1.11 g, 8 mmol) and
the reaction mixture was heated under reflux for 20 h. Workup as described
in GP II yielded a brownish foam (3.85 g). FC (CH2Cl2) yielded 4 (2.11 g,
61%) as white foam. M.p. 72.3 ± 73.48C; Rf (acetone/hexane 1:1): 0.62;
[a]RDT
ˆ
26.55 (c ˆ 1.0, CHCl3); 1H NMR (400 MHz): d ˆ 1.06 (s, 6H,
(4R,5R)-2,2-Dimethyl-a,a,a',a'-tetra(4-tert-butyldimethylsiloxyphenyl)-
2 CH3), 3.98 ± 4.02 (m, 2H, 2 OH), 4.49 (s, 2H, 2 CH), 4.92 (s, 4H,
2 CH2(G1)), 4.99 (s, 12H, 2 CH2(G1), 4 CH2(P)), 5.02 (s, 8H, 4 CH2(P)),
6.54 (t, J ˆ 2.3, 2H, 2 arom. H(G1)), 6.57 (t, J ˆ 2.3, 2H, 2 arom. H(G1)),
6.63 (d, J ˆ 2.3, 4H, 4 arom. H(G1)), 6.70 (d, J ˆ 2.3, 4H, 4 arom. H(G1)),
6.80 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 6.91 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.20 ±
7.47 (m, 44H, 4 arom. H(c), 40 arom. H(P)); 13C NMR (100 MHz): d ˆ 27.2,
69.8, 69.9, 70.1, 77.6, 81.1, 101.5, 101.6, 106.3, 106.4, 109.2, 113.5, 114.3, 127.6,
128.0, 128.6, 128.9, 129.7, 135.4, 136.8, 138.7, 139.5, 157.8, 157.9, 160.1, 160.2;
1,3-dioxolane-4,5-dimethanol (1): Following the usual procedure,[21]
a
solution of 4-tert-butyldimethylsilyloxy phenyl bromide (11.5 g, 40 mmol)
in THF (15 mL) was added over 20 min to Mg (1.0 g, 40 mmol) and a few
iodine crystals. This mixture was heated under reflux for 1 h before a
solution of (R,R)-dimethyl-O,O-methylidene tartrate (2.0 g, 8 mmol) in
THF (15 mL) was added over 20 min. After heating under reflux for 3 h
and stirring overnight at RT, the milky brown reaction mixture was
neutralized with saturated NH4Cl solution (40 mL). Et2O was added,
washed with saturated NaCl solution (3 Â ) and the combined aqueous
layers were extracted (3 Â Et2O). After drying of the combined organic
layers over MgSO4 and evaporation of the solvent, the crude product was
dried under high vacuum to yield an orange foam (10.0 g). FC (CH2Cl2)
yielded the product (6.23 g, 79%) as a yellowish foam. This was dissolved in
Et2O (60 mL) and MeOH (30 mL), then most of the Et2O was evaporated,
and the flask was put in the refrigerator overnight to give MeOH-
containing colorless crystals, which, after drying under high vacuum (24 h,
708C), yielded solvent-free 1 (4.82 g, 61%) as a white solid. M.p. 182.8 ±
IR (CHCl3): nÄ ˆ 3008w, 1597s, 1508s, 1454m, 1374m, 1294w, 1160s,
1
1056m, 1028m, 836w cm
; MALDI-TOF MS (CCA): m/z: 1763.7
‡
([M‡Na] ); C115H102O16 (1740.06): calcd C 79.38, H 5.91; found C 79.31,
H 5.90.
(Bn)16 {[G2]F}4 [Phe-TADDOL] (5): As described in GP II, a solution of
[15]
Â
second-generation Frechet-type branch bromide
(6.46 g, 8 mmol) in
acetone (20 mL) was added to a solution of TADDOL 2 (1.06 g, 2 mmol) in
acetone (20 mL). To this solution was added K2CO3 (1.11 g, 8 mmol) and
the reaction mixture was heated to 408C for 30 h. Workup as in GP II
yielded a brownish foam (7.51 g). Two FC (CH2Cl2) yielded 5 (5.95 g, 87%)
as a white foam. M.p. 71.4 ± 75.6 (glass CH2(G2)), 4.97 (s, 16H, 8 CH2), 4.98
(s, 16H, 8 CH2(P)), 6.49 ± 6.56 (m, 12H, 4 arom. H(G1), 8 arom. H(G2)),
6.59 (d, J ˆ 2.2, 4H, 4 arom. H(G1)), 6.63 (d, J ˆ 2.3, 8H, 8 arom. H(G2)),
6.66 (d, J ˆ 2.3, 8H, 8 arom. H(G2)), 6.66 (d, J ˆ 2.2, 4H, 4 arom. H(G1)),
6.78 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 6.88 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.19
(d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.22 ± 7.39 (m, 80H, 80 arom. H(P)), 7.41 (d,
J ˆ 9.0, 4H, 4 arom. H(c)); 13C NMR (125 MHz): d ˆ 27.2, 69.8, 69.9, 70.0,
70.1, 77.5, 101.5, 101.6, 101.7, 106.2, 106.3, 106.4, 106.5, 109.1, 113.5, 114.3,
127.5, 127.6, 127.9, 128.0, 128.5, 128.6, 128.9, 129.7, 135.3, 136.8, 138.6, 139.2,
139.5, 157.8, 157.9, 160.0, 160.1, 160.2; IR (CHCl3): nÄ ˆ 3374w, 3009w, 1596s,
1508w, 1453m, 1374m, 1295m, 1158s, 1054m, 835.2w cm 1; MALDI-TOF
183.48C; Rf (acetone/hexane 1:4): 0.46; [a]DRT
ˆ
34.6 (c ˆ 1.1, CHCl3);
1H NMR (400 MHz): d ˆ 0.17 (s, 12H, 4 CH3Si), 0.21 (s, 12H, 4 CH3Si),
0.96 (s, 18H, 2 tBu), 0.99 (s, 18H, 2 tBu), 3.91 ± 3.94 (m, 2H, 2 OH), 4.44 (s,
2H, 2 CH), 6.71 (d, J ˆ 8.8, 4H, 4 arom. H), 6.79 (d, J ˆ 8.8, 4H, 4 arom. H),
7.18 (d, J ˆ 8.7, 4H, 4 arom. H), 7.36 (d, J ˆ 8.7, 4H, 4 arom. H); 13C NMR
(100 MHz): d ˆ 4.4, 4.3, 18.2, 18.3, 25.7, 27.1, 77.7, 81.1, 109.2, 118.8,
119.4, 128.8, 129.8, 135.6, 139.0, 154.7, 154.9; IR (CHCl3): nÄ ˆ 3352w,
2957m, 2931m, 2859m, 1711w, 1606m, 1507s, 1472w, 1362w, 1257s, 1054w,
914s, 842s cm 1; MALDI-TOF MS (2,5-DHB): m/z: 1011.3 ([M‡Na] );
‡
C55H86O8Si4 (987.62): calcd C 66.89, H 8.78; found C 66.95, H 8.78.
(4R,5R)-2,2-Dimethyl-a,a,a',a'-tetra(4-hydroxyphenyl)-1,3-dioxolane-4,5-
dimethanol (2): As described in GP I, TBAF (6.39 g, 20 mmol) was added
to a solution of 1 (5.0 g, 5 mmol) in THF (90 mL). In the brownish-red
suspension a red lump formed after a few minutes, which slowly dissolved
again after stirring for 40 h at RT. Workup as in GP I yielded an orange
foam (3.60 g) as crude product. FC (acetone/CH2Cl2 1:2) yielded 2 (2.32 g,
87%) as a slightly yellow solid. M.p. > 1808C (decomp), 214.2 ± 215.0 (liq);
Rf (acetone/hexane 1:1): 0.32; 1H NMR (400 MHz): d ˆ 1.01 (s, 6H, 2 CH3),
4.33 (s, 2H, 2 CH), 6.65 (d, J ˆ 8.9, 2H, 2 arom. H), 6.75 (d, J ˆ 8.9, 2H, 2
arom. H), 7.09 (d, J ˆ 8.9, 2H, 2 arom. H), 7.33 (d, J ˆ 8.9, 2H, 2 arom. H);
13C NMR (100 MHz): d ˆ 27.4, 78.3, 82.5, 109.6, 114.6, 115.3, 130.4, 131.2,
135.0, 138.7, 157.4, 157.5. Because of its polar nature, the product could not
be isolated entirely from the solvent and was used directly for the next
reaction steps.
‡
MS (THA): m/z: 3461.6 ([M‡Na] ); C227H198O32 (3438.04): calcd C 79.30,
H 5.80; found C 79.04, H 5.85.
(Bn)32 {[G3]F}4 [Phe-TADDOL] (6): As described in GP II, a solution of
[15]
Â
third-generation Frechet-type branch bromide
(4.64 g, 2.8 mmol) in
acetone (15 mL) was added to a solution of TADDOL 2 (0.37 g, 0.7 mmol)
in acetone (15 mL). K2CO3 (0.39 g, 2.8 mmol) was added to this solution
and the reaction mixture was heated to 508C for 3 d. Workup as described
in GP II yielded a brownish foam (5.56 g). FC (2 Â CH2Cl2) yielded 6
(4.00 g, 84%) as a white foam. M.p. 76.4 ± 78.08C (glass), from ca. 908C
liquid; Rf (acetone/hexane 1:1): 0.42; [a]DRT
ˆ
6.40 (c ˆ 1.00, CHCl3);
1H NMR (500 MHz): d ˆ 0.99 (s, 6H, 2 CH3), 4.15 (s, 2H, 2 OH), 4.42 (s,
2H, 2 CH), 4.79 ± 4.94 (m, 120H, 60 CH2), 6.46 ± 6.54 (m, 28H, 4 arom.
H(G1), 8 arom. H(G2), 16 arom. H(G3)), 6.57 ± 6.63 (m, 56H, 8 arom.
H(G1), 16 arom. H(G2), 32 arom. H(G3)), 6.73 (d, J ˆ 9.0, 4H, 4 arom.
H(c)), 6.84 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.19 (d, J ˆ 9.0, 4H, 4 arom. H(c)),
7.21 ± 7.35 (m, 160H, 160 arom. H(P)), 7.38 (d, J ˆ 9.0, 4H, 4 arom. H(c));
13C NMR (125 MHz): d ˆ 27.2, 69.7, 69.9, 70.0, 101.6, 106.3, 106.4, 106.5,
114.2, 127.5, 127.6, 127.7, 127.9, 128.0, 128.3, 128.4, 128.5, 128.9, 136.8, 139.2,
139.5, 160.0, 160.1; IR (CHCl3): nÄ ˆ 3008w, 2875w, 1596s, 1498w, 1453m,
1374m, 1296m, 1158s, 1056m, 836w cm 1; MALDI-TOF MS (IAA): m/z:
(Bn)4 {[G0]}4 [Phe-TADDOL] (3): Benzyl bromide (0.645 g, 3.77 mmol)
was added to a solution of TADDOL 2 (0.503 g, 0.95 mmol) in DMF
(10 mL). To this solution was added dried and finely powdered K2CO3
(0.52 g, 3.77 mmol), and the resulting suspension was stirred for 18 h at RT,
then heated under reflux for 1 h. After cooling to RT, H2O (20 mL) and
CH2Cl2 (40 mL) were added, and the solids were filtered off and rinsed with
CH2Cl2. The two layers of the filtrate were separated, and the aqueous
layer was extracted twice with CH2Cl2. The combined organic layers were
washed with H2O, then dried over MgSO4, and the solvent was evaporated
to yield the crude product as a yellow oil. FC (CH2Cl2) yielded 3 (0.50 g,
59%) as a white solid. M.p. 176.6 ± 177.88C; Rf (acetone/hexane 1:2): 0.31;
‡
3390.4, 6857.6 ([M‡Na] ), 7159.1, 7584.5, 8434.1; C451H390O64 (6834.00):
calcd C 79.26, H 5.75; found C 79.20, H 5.78.
(Bn)64 {[G4]F}4 [Phe-TADDOL] (7): As described in GP II, a solution of
[15]
Â
fourth-generation Frechet-type branch bromide (5.42 g, 1.62 mmol) in
[a]RDT
ˆ
49.24 (c ˆ 1.1, CHCl3); 1H NMR (500 MHz): d ˆ 1.05 (s, 6H,
acetone (15 mL) was added to
a
solution of TADDOL
2
(0.214 g,
Chem. Eur. J. 1999, 5, No. 11
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3231

D. Seebach and P. B. Rheiner
FULL PAPER
0.404 mmol) in acetone (10 mL). To this solution was added K2CO3
(0.223 g, 1.62 mmol) and the reaction mixture was heated to 508C for 4 d.
Workup as described in GP II yielded a brownish foam (5.79 g). Two FC
(CH2Cl2) yielded 7 (1.21 g, 22%) as a white foam (the difficult identi-
fication of the product led to a big loss of product after the first column
chromatography). M.p. 77.3 ± 78.18C (glass), from ca. 908C liquid. Rf
C(2)), 2.80 (ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-C(2)), 3.42 (ªddº, ABX,
J ˆ 9.4, 5.6, 1H, H-C(1)), 3.48 (ªddº, ABX, J ˆ 9.4, 5.2, 1H, H-C(1)), 3.67 ±
3.72 (m, 1H, H-C(3)), 4.40 ± 4.44, 4.55 ± 4.59 (m, 4H, 2 OCH2Ph), 4.47 (s,
2H, CH2Br), 7.08 (d, J ˆ 8.1, 2H, 2 arom. H), 7.22 ± 7.34 (m, 12H, 12 arom.
H); 13C NMR (100 MHz): d ˆ 16.6, 33.3, 33.7, 46.2, 69.1, 70.8, 73.0, 74.6,
127.4, 127.5, 127.6, 128.3, 128.5, 129.0, 129.6, 135.2, 138.6, 139.1, 141.6; IR
(CHCl3): nÄ ˆ 3002w, 1714s, 1603w, 1452m, 1316m, 1277s, 1115m, 1070m,
(acetone/hexane 1:1): 0.41; [a]DRT
ˆ
3.36 (c ˆ 1.00, CHCl3); 1H NMR
‡
(500 MHz): d ˆ 0.94 (s, 6H, 2 CH3), 4.26 (brs, 2H, 2 OH), 4.38 (s, 2H,
2 CH), 4.74 ± 4.82 (m, 120H, 4 CH2(G1), 8 CH2(G2), 16 CH2(G3),
32 CH2(G4)), 4.82 ± 4.88 (m, 128H, 64 CH2(P)), 6.43 ± 6.48 (m, 60H, 4
arom. H(G1), 8 arom. H(G2), 16 arom. H(G3), 32 arom. H(G4)), 6.53 ±
6.60 (m, 120H, 8 arom. H(G1), 16 arom. H(G2), 32 arom. H(G3), 64 arom.
H(G4)), 6.68 (d, J ˆ 8.2, 4H, 4 arom. H(c)), 6.79 (d, J ˆ 8.2, 4H, 4 arom
H(c)), 7.14 (d, J ˆ 7.7, 4H, 4 arom. H(c)), 7.17 ± 7.30 (m, 320H, 320 arom.
H(P)), 7.36 (d, J ˆ 7.7, 4H, 4 arom. H(c)); 13C NMR (125 MHz): d ˆ 27.2,
69.9, 70.0, 101.6, 106.4, 127.3, 127.5, 127.6, 127.7, 127.9, 128.0, 128.3, 128.4,
128.5, 136.8, 139.2, 139.4, 160.0, 160.1; IR (CHCl3): nÄ ˆ 3008w, 2876w,
1596s, 1498w, 1452m, 1373m, 1296m, 1158s, 1055m, 834w cm 1; MALDI-
1026w, 910w cm 1; MS (EI): m/z: 453 (0.4, [M] ), 265 (18), 175 (10), 159
(12), 158 (6), 147 (7), 145 (8), 144 (8), 131 (10), 117 (11), 105 (13), 104 (17),
92 (12), 91 (100); C26H29O2Br (453.42): calcd C 68.87, H 6.45; found C 68.93,
H 6.45.
(Bn)4 [G1]F [G1]*(A) OTBDPS (15): As described in GP III, NaH
(1.28 g, 53.4 mmol) was added to THF (20 mL). After cooling to ice-bath
temperature, a solution of diol 11 (4.0 g, 8.9 mmol) in THF (20 mL) was
added and the reaction mixture was stirred at RT for 1 h, before a solution
[15]
Â
of first-generation Frechet-type branch bromide (8.2 g, 21.4 mmol) in
THF (20 mL) was added slowly. After stirring at RT for 3 h, the reaction
mixture was heated under reflux for 15 h. Workup as described in GP III
yielded a brownish oil (10.6 g). FC (acetone/hexane 1:1000) yielded 15
‡
TOF MS (IAA): m/z: 6856.4, 13647.6 ([M‡Na] ), 13950.4; C899H774O128
(13625.93): calcd C 79.25, H 5.73; found C 79.03, H 5.76.
(7.8 g, 83%) as a clear viscous oil. Rf (acetone/hexane 1:3): 0.35; [a]DRT
ˆ
The preparation of compounds 8[35] and 9 ± 11[16] is described in previous
publications. The compounds ent-8, ent-10 and ent-11 were synthesized
following the same procedures as for their enantiomers. Analytical data
correspond with the literature.
1.46 (c ˆ 1.01, CHCl3); 1H NMR (400 MHz): d ˆ 1.09 (s, 9H, tBu), 1.21 (d,
J ˆ 6.3, 3H, CH3-C(3)), 2.04 ± 2.14 (m, 1H, H-C(2)), 2.58 ± 2.67 (m, 2H,
PhCH2-C(2)), 2.74 ± 2.83 (m, 2H, PhCH2-C(2)), 3.38 ± 3.53 (m, 1H,
H-C(1)), 3.64 ± 3.72 (m, 1H, H-C(3)), 4.31 ± 4.53 (m, 4H, 2 OCH2Ph
(G2)), 4.73 (s, 2H, CH2OSi), 4.98 (d, J ˆ 5.6, 8H, 4 OCH2Ph (P)), 6.50 ± 6.54
(m, 2H, 2 arom. H (G2)), 6.57 (d, J ˆ 2.3, 2H, 2 arom. H (G2)), 6.61 (d, J ˆ
2.3, 2H, 2 arom. H (G2)), 7.10 (d, J ˆ 8.1, 2H, 2 arom. H (G1)), 7.22 (d, J ˆ
7.6, 2H, 2 arom. H (G1)), 7.24 ± 7.43 (m, 26H, 26 arom. H (P)), 7.67 ± 7.72 (m,
4H, 4 arom. H (P)); 13C NMR (100 MHz): d ˆ 16.8, 19.3, 26.9, 33.1, 46.3,
65.4, 69.3, 70.0, 70.7, 72.9, 74.7, 101.1, 106.3, 126.0, 127.5, 127.7, 127.9, 128.5,
129.0, 129.6, 133.6, 135.6, 136.9, 138.5, 139.6, 141.2, 141.7, 160.0; IR (CHCl3):
nÄ ˆ 3007w, 2932w, 2860w, 1596s, 1453w, 1376m, 1293w, 1157s, 1060m,
(Bn)2 [G1]*(A) OTBDPS (12): As described in GP III, NaH (1.28 g,
53.4 mmol) was added to THF (20 mL). After cooling to ice-bath temper-
ature, a solution of diol 11 (4.0 g, 8.9 mmol) in THF (20 mL) was added and
the reaction mixture was stirred at 08C for 1 h before a solution of benzyl
bromide (3.66 g, 21.4 mmol) in THF (20 mL) was added slowly. After
stirring at RT for 30 min, the reaction mixture was heated under reflux for
15 h. Workup as described in GP III yielded a slightly yellow oil (9.1 g). FC
(acetone/hexane 1:3) yielded 12 (5.31 g, 95%) as a clear viscous oil. Rf
1
‡
(acetone/hexane 1:3): 0.46; [a]DRT
ˆ
2.1 (c ˆ 1.05, CHCl3); 1H NMR
832w cm
;
MALDI-TOF MS (Dithranol): m/z: 1076.5 ([M‡Na] );
C70H72O7Si (1053.42): calcd C 79.81, H 6.89; found C 79.59, H 6.88.
(400 MHz): d ˆ 1.10 (s, 9H, tBu), 1.23 (d, J ˆ 6.3, 3H, CH3-C(3)), 2.09 ± 2.16
(m, 1H, H-C(2)), 2.63 (ªddº, ABX, J ˆ 13.5, 8.9, 1H, PhCH2-C(2)), 2.82
(ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-C(2)), 3.44 (ªddº, ABX, J ˆ 9.4, 5.1,
1H, H-C(1)), 3.70 ± 3.76 (m, 1H, H-C(3)), 4.41 ± 4.45, 4.57 ± 4.60 (m, 4H,
2 OCH2Ph), 4.75 (s, 2H, CH2OSi), 7.09 (d, J ˆ 8.0, 2H, 2 arom. H), 7.20 ±
7.44 (m, 18H, 18 arom. H), 7.69 ± 7.71 (m, 4H, 4 arom. H); 13C NMR
(100 MHz): d ˆ 16.7, 19.3, 26.9, 33.2, 46.3, 65.4, 69.2, 70.8, 73.0, 74.7, 125.9,
127.4, 127.6, 127.7, 128.3, 129.0, 129.7, 133.6, 135.6, 138.5, 138.7, 139.2, 139.7;
IR (CHCl3): nÄ ˆ 3007w, 2932w, 2859w, 1711s, 1454w, 1428w, 1363m,
(Bn)4 [G1]F [G1]*(A) OH (16): As described in GP I, TBAF (6.3 g,
20 mmol) was added to a solution of 15 (6.0 g, 5.7 mmol) in THF (75 mL).
Workup as described in GP I yielded 16 as a slightly yellow oil (6.0 g). A
small amount thereof was purified for analytical data by FC, the rest was
used for further reaction steps. Rf (Et2O/pentane 1:3): 0.43; [a]DRT
ˆ
3.5
(c ˆ 1.50, CHCl3); 1H NMR (400 MHz): d ˆ 1.20 (d, J ˆ 6.4, 3H, CH3-C(3)),
1.62 ± 1.70 (m, 1H, OH), 2.04 ± 2.13 (m, 1H, H-C(2)), 2.61 (ªddº, ABX, J ˆ
13.5, 8.9, 1H, PhCH2-C(2)), 2.79 (ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-
C(2)), 3.40 (ªddº, ABX, J ˆ 9.4, 5.6, 1H, H-C(1)), 3.46 (ªddº, ABX, J ˆ 9.4,
5.1, 1H, H-C(1)), 3.63 ± 3.71 (m, 1H, H-C(3)), 4.29 ± 4.53 (m, 4H,
2 OCH2Ph (G2)), 4.59 (d, J ˆ 3.4, 2H, CH2OH), 6.50 ± 6.55 (m, 4H, 4
arom. H (G2)), 6.59 (d, J ˆ 2.3, 2H, 2 arom. H (G2)), 7.22 (d, J ˆ 8.4, 2H, 2
arom. H (G1)), 7.26 ± 7.41 (m, 20H, 20 arom. H (P)); 13C NMR (100 MHz):
d ˆ 16.7, 33.2, 46.1, 65.2, 69.2, 70.0, 70.7, 72.8, 74.8, 101.0, 101.1, 106.4, 106.5,
127.1, 127.5, 127.9, 128.5, 129.3, 136.9, 138.3, 140.5, 141.1, 141.6, 159.9; IR
(CHCl3): nÄ ˆ 3008w, 1710s, 1596s, 1453m, 1364s, 1292w, 1156s, 1055m,
‡
1112m, 1090m, 1020w, 824w cm 1; MS (EI): m/z: 627 (5, [M 1] ), 479 (6),
404 (8), 403 (23), 373 (14), 301 (7), 297 (16), 295 (7), 269 (8), 265 (18), 247
(19), 241 (5), 237 (6), 236 (20), 235 (100), 199 (25), 181 (9), 157 (8), 91 (31).
(Bn)2 [G1]*(A) OH (13): As described in GP I, TBAF (6.65 g,
21.1 mmol) was added to a solution of 12 (5.31 g, 8.44 mmol) in THF
(90 mL). Workup as described in GP I yielded a brown oil (5.4 g). FC
(acetone/hexane 1:3) yielded 13 (2.92 g, 89%) as a slightly yellow oil. Rf
(acetone/hexane 1:3): 0.28; [a]DRT
ˆ
6.90 (c ˆ 1.12, CHCl3); 1H NMR
‡
835w cm 1; MS (FAB): m/z: 816 (11), 815 (33, [M] ), 814 (54), 607 (11), 606
(400 MHz): d ˆ 1.22 (d, J ˆ 6.4, 3H, CH3-C(3)), 1.68 (t, J ˆ 5.7, 1H, OH),
2.07 ± 2.14 (m, 1H, H-C(2)), 2.64 (ªddº, ABX, J ˆ 13.5, 8.9, 1H, PhCH2-
C(2)), 2.81 (ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-C(2)), 3.42 (ªddº, ABX,
J ˆ 9.4, 5.6, 1H, H-C(1)), 3.49 (ªddº, ABX, J ˆ 9.4, 5.2, 1H, H-C(1)), 3.68 ±
3.74 (m, 1H, H-C(3)), 4.40 ± 4.44, 4.56 ± 4.59 (m, 4H, 2 OCH2Ph), 4.63 (d,
J ˆ 5.3, 2H, CH2OH), 7.11 (d, J ˆ 8.1, 2H, 2 arom. H), 7.22 ± 7.34 (m, 12H,
12 arom. H); 13C NMR (100 MHz): d ˆ 16.7, 33.2, 46.3, 65.3, 69.2, 70.8, 73.0,
74.6, 127.1, 127.4, 127.6, 128.3, 129.4, 138.3, 138.7, 139.1, 140.7; IR (CHCl3):
nÄ ˆ 3605w, 3457br, 3008m, 2870m, 1810w, 1722w, 1602w, 1513w, 1496m,
1454s, 1378m, 1090s, 1028m, 1012m, 913w, 820w cm 1; MS (EI): m/z:
(41), 605 (94), 604 (12), 603 (24), 515 (14), 514 (10), 513 (24), 495 (12), 423
(12), 393 (22), 304 (44), 303 (100), 213 (19), 181 (31), 121 (19), 105 (21);
C54H54O7 (815.02): calcd C 79.58, H 6.68; found C 79.69, H 6.94.
(Bn)4 [G1]F [G1]*(A) Br (17): As described in GP IV, PPh3 (2.82 g,
10.7 mmol) and CBr4 (3.57 g, 10.7 mmol) were added to a solution of
alcohol 16 (5.8 g, 7.12 mmol) in THF (75 mL). Workup as described in
GP IV yielded a slightly yellow oil (5.7 g). FC (Et2O/pentane 1:5) yielded
17 (2.95 g, 47% over two steps) as a colorless oil. Rf (acetone/hexane 1:3):
0.34; [a]RDT
ˆ
1.33 (c ˆ 1.50, CHCl3); 1H NMR (400 MHz): d ˆ 1.20 (d, J ˆ
‡
391.2 (0.3, [M‡1] ), 299 (6), 282 (14), 252 (6), 227 (22), 191 (15), 176 (46),
6.3, 3H, CH3-C(3)), 2.02 ± 2.12 (m, 1H, H-C(2)), 2.56 ± 2.66 (m, 1H, PhCH2-
C(2)), 2.72 ± 2.81 (m, 1H, PhCH2-C(2)), 3.36 ± 3.50 (m, 1H, H-C(1)), 3.62 ±
3.70 (m, 1H, H-C(3)), 4.28 ± 4.53 (m, 6H, 2 OCH2Ph(G2) and CH2Br), 4.99
(d, J ˆ 5.0, 8H, 4 OCH2Ph(P)), 6.50 ± 6.53 (m, 2H, 2 arom. H(G2)), 6.55 (d,
J ˆ 2.2, 2H, 2 arom. H(G2)), 6.59 (d, J ˆ 2.3, 2H, 2 arom. H(G2)), 7.05 ± 7.12
(m, 2H, 2 arom. H(G1)), 7.21 ± 7.25 (m, 2H, 2 arom. H(G1)), 7.26 ± 7.41 (m,
20H, 20 arom. H(P)); 13C NMR (100 MHz): d ˆ 16.7, 33.2, 33.7, 46.1, 46.2,
69.2, 70.0, 70.7, 72.9, 74.6, 101.0, 101.1, 106.4, 106.5, 127.5, 127.9, 128.5, 129.0,
175 (21), 161 (19), 148 (12), 147 (18), 145 (22), 144 (23), 135 (16), 134 (11),
131 (30), 121 (18), 117 (24), 92 (11), 91 (100); C26H30O3 (390.52): calcd C
79.97, H 7.74; found C 80.10, H 7.54.
(Bn)2 [G1]*(A) Br (14): As described in GP IV, PPh3 (2.9 g, 11 mmol)
and CBr4 (3.7 g, 11 mmol) were added to a solution of alcohol 13 (2.92 g,
7.47 mmol) in THF (40 mL). Workup as described in GP IV yielded a
slightly yellow oil (8.84 g). FC (acetone/hexane 1:19) yielded 14 (1.56 g,
28%) as a colorless oil. Rf (acetone/hexane 1:9): 0.64; [a]RDT ˆ ‡16.91 (c ˆ
1.20, CHCl3); 1H NMR (400 MHz): d ˆ 1.22 (d, J ˆ 6.4, 3H, CH3-C(3)),
2.08 ± 2.13 (m, 1H, H-C(2)), 2.63 (ªddº, ABX, J ˆ 13.5, 8.9, 1H, PhCH2-
129.5, 129.6, 134.9, 135.2, 136.9, 141.1, 141.5, 160.0; IR (CHCl3): nÄ ˆ 3008m,
1
2870w, 1597s, 1498w, 1453m, 1375m, 1292w, 1157s, 1048m, 833w cm
;
‡
MS (FAB): m/z: 878 (15, [M] ), 877 (10), 876 (12), 832 (11), 606 (24), 605
3232
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0511-3232 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 11

Dendritic TADDOLs
3221±3236
(49), 393 (14), 319 (15), 305 (14), 304 (63), 303 (100), 213 (36), 212 (12), 211
(25), 183 (15), 182 (13), 181 (61), 175 (15), 167 (14), 165 (17), 155 (20), 154
(49), 152 (13), 141 (14), 139 (23), 138 (20), 137 (28), 136 (45), 131 (18), 129
(16), 117 (15), 115 (17), 107 (29), 105 (40), 104 (24); C54H53O6Br (877.91):
calcd C 73.88, H 6.08; found C 75.43, H 6.27.
H(G1) and 80 arom. H(P)); 13C NMR (100 MHz): d ˆ 16.8, 27.2, 33.3, 46.2,
69.2, 69.9, 70.0, 70.7, 72.9, 74.7, 77.6, 101.1, 106.4, 106.5, 113.4, 114.2, 127.5,
127.7, 127.8, 127.9, 128.6, 129.4, 129.8, 134.3, 134.4, 136.9, 141.0, 141.2, 141.6,
160.0; IR (CHCl3): nÄ ˆ 3008w, 2869w, 1596s, 1508m, 1453m, 1375m,
1293m, 1157s, 1055m, 834w cm 1; MALDI-TOF MS (HABA): m/z: 3741.3
‡
([M‡Na] ); C247H238O32 (3718.58): calcd C 79.78, H 6.45; found C 79.51, H
The compounds ent-15, ent-16 and ent-17 were synthesized following the
same procedures as for their enantiomers, and the analytical data
correspond.
6.40.
(Octyl)2 [G1]F COOMe (21): n-Octyl bromide (96 mL, 550 mmol), 18-C-
6 (11.6 g, 44 mmol), and K2CO3 (76.0 g, 550 mmol) were added to a solution
of methyl a-resorcylate (37.0 g, 220 mmol) in acetone (1 L), and the
reaction mixture was heated under reflux for 60 h. After cooling to RT the
solids were filtered off, and the solvent of the filtrate was evaporated. After
addition of CH2Cl2 (400 mL) the product was washed with H2O (200 mL)
and the aqueous layer was extracted again with CH2Cl2 (2 Â 400 mL). The
combined organic layers were dried over MgSO4 and the solvent removed
to yield a yellow oil. This was placed in the refrigerator overnight, where a
white product cristallized. The solid was redissolved in Et2O and the
insoluble parts were filtered off. The solvent of the filtrate was again
evaporated to give 21 as a white solid in quantitative yield. M.p. 40.8 ±
41.48C; Rf (CH2Cl2): 0.64; 1H NMR (300 MHz): d ˆ 0.89 (t, J ˆ 6.80, 6H,
2 CH3), 1.28 ± 1.48 (m, 20H, 10 CH2), 1.72 ± 1.82 (m, 4H, 2 CH2CH2O), 3.90
(s, 3H, OCH3), 3.97 (t, J ˆ 6.55, 4H, 2 CH2O), 6.63 (t, J ˆ 2.34, 1H, 1 arom.
H), 7.16 (d, J ˆ 2.34, 2H, 2 arom. H); 13C NMR (75 MHz): d ˆ 14.2, 22.7,
26.1, 29.3, 29.4, 31.8, 52.2, 68.4, 106.7, 107.7, 131.9, 160.2, 167.0; IR (CHCl3):
nÄ ˆ 2927s, 2858m, 1718m, 1596m, 1447m, 1352m, 1301m, 1167m, 1112s,
(Bn)8 {[G1]F [G1]*(A)}4 [Phe-TADDOL] (18): As described in GP II, a
solution of 14 (1.10 g, 2.43 mmol) in acetone (15 mL) was added to a
solution of TADDOL 2 (0.292 g, 0.55 mmol) in acetone (15 mL). To this
solution was added K2CO3 (0.336 g, 2.43 mmol), and the reaction mixture
was heated under reflux for 12 h. Workup as described in GP II yielded a
slightly yellow oil (1.15 g). FC (acetone/hexane 1:4) yielded 18 (0.45 g,
41%) as a colorless oil. Rf (acetone/hexane 1:4): 0.21; [a]DRT
ˆ
29.10 (c ˆ
1.10, CHCl3); 1H NMR (300 MHz): d ˆ 1.08 (s, 6H, (CH3)2-C(2)(c)), 1.22 ±
1.26 (m, 12H, 4 CH3-C(3)(G1)), 2.10 ± 2.19 (m, 4H, 4 H-C(2)(G1)), 2.61 ±
2.72 (m, 4H, 4 PhCH2-C(2)(G1)), 2.79 ± 2.89 (m, 4H, 4 PhCH2-C(2)(G1)),
3.42 ± 3.58 (m, 8H, 8 H-C(2)(G1)), 3.69 ± 3.77 (m, 4H, 4 H-C(3)(G1)), 4.02
(brs, 2H, 2 OH), 4.37 ± 4.61 (m, 18H, 8 CH2(P) and H-C(4), H-C(5)(c)),
4.98 (s, 4H, 2 CH2O(G1)), 5.03 (s, 4H, 2 CH2O(G1)), 6.88 (d, J ˆ 8.7, 4H, 4
arom. H(c)), 6.96 (d, J ˆ 8.7, 4H, 4 arom. H(c)), 7.13 (d, J ˆ 8.1, 4H, 4 arom.
H(c)), 7.21 ± 7.41 (m, 56H, 16 arom. H(G1) and 40 arom. H(P)), 7.42 (d, J ˆ
8.1, 4H, 4 arom. H(c)); 13C NMR (75 MHz): d ˆ 16.7, 27.2, 33.3, 46.2, 69.1,
69.9, 70.8, 73.0, 74.6, 75.7, 113.4, 114.2, 127.4, 127.5, 127.6, 127.8, 128.3, 128.9,
129.4, 129.7, 134.3, 138.6, 139.1, 141.1, 158.1, 168.6; IR (CHCl3): nÄ ˆ 3374br,
3007m, 2864w, 1607m, 1508s, 1454m, 1379m, 1090s, 1017m, 909s,
‡
1056w, 963m cm 1; MS (EI): m/z: 392 (34.7, [M] ), 364 (6), 361 (4), 280
(10), 248 (4), 221 (4), 181 (4), 168 (100), 137 (16), 111 (5), 83 (5), 69 (18), 57
(20), 43 (27), 28 (7); C24H40O4 (392.57): calcd C 73.43, H 10.27; found C
73.54, H 10.16.
1
‡
836m cm
;
MALDI-TOF MS (HABA): m/z: 2043.9 ([M‡Na] );
C135H142O16 (2020.60): calcd C 80.25, H 7.08; found C 79.33, H 6.92.
(Octyl)2 [G1]F OH (22): A solution of 21 (102.0 g, 0.26 mol) in Et2O
(450 mL) was added to a suspension of LiAlH4 (11.0 g, 0.29 mol) in Et2O
(350 mL) over 30 min. The grey mixture was heated under reflux for 4 h
and stirred overnight at RT. Hydrolysis by dropwise addition of H2O
(11 mL) followed by 15% NaOH solution (11 mL) and then once more by
H2O (33 mL) gave a clear supernatant solution, which was separated from
the salt. The organic layer was washed (2 Â H2O) and the combined
aqueous layers extracted (2 Â Et2O). The combined organic layers were
dried over MgSO4 and the solvent was evaporated to give a crude product
containing 22 as a colorless oil (107.1 g). A small amount thereof was
purified by FC (CH2Cl2) for analytical purposes, the rest was used directly
for the next reaction steps. Rf (CH2Cl2): 0.18; 1H NMR (300 MHz): d ˆ 0.89
(t, J ˆ 6.8, 6H, 2 CH3), 1.21 ± 1.49 (m, 20H, 10 CH2), 1.71 ± 1.80 (m, 4H,
2 CH2CH2O), 1.98 (t, J ˆ 6.0, 1H, OH), 3.92 (t, J ˆ 6.6, 4H, 2 CH2O), 4.59
(d, J ˆ 5.8, 2H, CH2OH), 6.36 (t, J ˆ 2.3, 1H, 1 arom. H), 6.48 (d, J ˆ 2.2,
2H, 2 arom. H); 13C NMR (75 MHz): d ˆ 14.1, 22.7, 26.1, 29.3, 29.4, 31.8,
65.4, 68.1, 100.6, 105.1, 143.2, 160.5; IR (CHCl3): nÄ ˆ 3604w, 2926s, 2856s,
1596s, 1454s, 1384m, 1293m, 1165s, 1061m, 836w cm 1; MS (EI): m/z: 364
(Bn)16 {[G1]F [G1]*(A)}4 [Phe-TADDOL] (19): As described in GP II, a
solution of 17 (2.20 g, 2.51 mmol) in acetone (5 mL) was added to a solution
of TADDOL 2 (0.302 g, 0.57 mmol) in acetone (20 mL). To that was added
K2CO3 (0.32 g, 2.28 mmol), and the reaction mixture was heated under
reflux for 45 h. Workup as described in GP II yielded a brownish foam
(2.73 g). FC (acetone/hexane 1:2) yielded 19 (1.70 g, 80%) as a slightly
yellow foam. Rf (acetone/hexane 2:3): 0.27; [a]DRT
ˆ
14.43 (c ˆ 0.98,
1
CHCl3); H NMR (500 MHz): d ˆ 1.06 (s, 6H, (CH3)2-C(2)(c)), 1.17 ± 1.22
(m, 12H, 4 CH3-C(3)(G1)), 2.03 ± 2.14 (m, 4H, 4 H-C(2)(G1)), 2.59 ± 2.68
(m, 4H, 4 PhCH2-C(2)(G1)), 2.75 ± 2.84 (m, 4H, 4 PhCH2-C(2)(G1)),
3.38 ± 3.51 (m, 8H, 8 H-C(2)(G1)), 3.62 ± 3.72 (m, 4H, 4 H-C(3)(G1)),
4.01 (brs, 2H, 2 OH), 4.28 ± 4.40 (m, 12H, 8 CH2(G2)), 4.46 ± 4.52 (m, 6H,
8 CH2(G2) and C(4), C(5)(c)), 4.88 ± 5.03 (m, 40H, 16 CH2(P) und 4
CH2O(G1)), 6.49 ± 6.53 (m, 8H, 8 arom. H(G2)), 6.53 ± 6.58 (m, 8H, 8
arom. H(G2)), 6.58 ± 6.61 (m, 8H, 8 arom. H(G2)), 6.84 (d, J ˆ 9.0, 4H, 4
arom. H(c)), 6.92 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.11 (d, J ˆ 8.1, 4H, 4 arom.
H(c)), 7.14 (d, J ˆ 8.1, 4H, 4 arom. H(c)), 7.21 ± 7.41 (m, 96H, 16 arom.
H(G1) and 80 arom. H(P)); 13C NMR (125 MHz): d ˆ 16.8, 23.5, 26.9, 27.2,
33.3, 46.2, 69.2, 69.9, 69.9, 70.0, 70.7, 72.9, 74.7, 76.8, 77.0, 77.3, 77.6, 101.1,
101.1, 106.4, 106.5, 113.4, 114.2, 126.5, 126.7, 126.9, 127.5, 127.7, 127.8, 127.9,
128.6, 128.9, 129.4, 129.7, 134.3, 134.4, 135.6, 136.9, 138.7, 141.0, 141.2, 141.6,
158.0, 158.1, 160.0; IR (CHCl3): nÄ ˆ 3008w, 2870w, 1596s, 1509w, 1454m,
1376m, 1293w, 1157s, 1058m, 833w cm 1; MALDI-TOF MS (CCA): m/z:
‡
(28.8, [M] ), 252 (7), 221 (6), 141 (46), 140 (100), 138 (10), 123 (15), 111
(21), 71 (14), 69 (24), 57 (26), 55 (23), 43 (28); C23H40O3 (364.56): calcd C
75.78, H 11.06; found C 75.88, H 10.94.
(Octyl)2 [G1]F Br (23): As described in GP IV, PPh3 (78.7 g, 0.3 mol), and
CBr4 (99.5 g, 0.3 mol) were added to a solution of alcohol 22 (88.0 g,
0.24 mol) in THF (650 mL). Workup as described in GP IV yielded a
yellow oil as crude product containing 23 (149 g). A small amount thereof
was purified by FC (CH2Cl2) for analytical purposes, the rest was used
directly for the next reaction steps. Rf (CH2Cl2): 0.85; 1H NMR (300 MHz):
d ˆ 0.89 (t, J ˆ 6.8, 6H, 2 CH3), 1.21 ± 1.50 (m, 20H, 10 CH2), 1.71 ± 1.83 (m,
4H, 2 CH2CH2O), 3.92 (t, J ˆ 6.6, 4H, 2 CH2O), 4.41 (s, 2H, CH2Br), 6.38
(t, J ˆ 2.2, 1H, 1 arom. H), 6.51 (d, J ˆ 2.2, 2H, 2 arom. H), 13C NMR
(75 MHz): d ˆ 14.1, 22.7, 26.1, 29.3, 29.4, 31.9, 33.8, 68.2, 101.5, 107.5, 139.6,
160.5; IR (CHCl3): nÄ ˆ 2928s, 2853s, 1595s, 1461s, 1384m, 1347m, 1167s,
‡
3741.7 ([M‡Na] ); C247H238O32 (3718.58): calcd C 79.78, H 6.45; found C
79.87, H 6.58.
(Bn)16 {[G1]F [G1]*(B)}4 [Phe-TADDOL] (20): As described in GP II, a
solution of ent-17 (1.89 g, 2.16 mmol) in acetone (5 mL) is added to a
solution of TADDOL 2 (0.29 g, 0.54 mmol) in acetone (15 mL). To this
solution was added K2CO3 (0.30 g, 2.16 mmol), and the reaction mixture
was heated under reflux for 45 h. Workup as described in GP II yielded a
brownish foam (2.3 g). FC (acetone/hexane 1:2) yielded 20 (1.53 g, 76%) as
a slightly yellow foam. Rf (acetone/hexane 2:3): 0.25; [a]DRT
ˆ
10.85 (c ˆ
‡
1056m cm 1; MS (EI): m/z: 428 (52.7 [M‡1] ), 426 (54), 348 (24), 347 (43),
1.10, CHCl3); 1H NMR (400 MHz): d ˆ 1.06 (s, 6H, (CH3)2-C(2)(c)), 1.19 ±
1.22 (m, 12H, 4 CH3-C(3)(G1)), 2.05 ± 2.12 (m, 4H, 4 H-C(2)(G1)), 2.59 ±
2.67 (m, 4H, 4 PhCH2-C(2)(G1)), 2.77 ± 2.82 (m, 4H, 4 PhCH2-C(2)(G1)),
3.38 ± 3.50 (m, 8H, 8 H-C(2)(G1)), 3.64 ± 3.71 (m, 4H, 4 H-C(3)(G1)), 3.99
(brs, 2H, 2 OH), 4.30 ± 4.38 (m, 12H, 8 CH2(G2)), 4.48 ± 4.52 (m, 6H,
8 CH2(G2) and C(4), C(5)(c)), 4.91 ± 4.99 (m, 40H, 16 CH2(P) and
4 CH2O(G1)), 6.50 ± 6.53 (m, 8H, 8 arom. H(G2)), 6.53 ± 6.56 (m, 8H, 8
arom. H(G2)), 6.59 ± 6.61 (m, 8H, 8 arom. H(G2)), 6.84 (d, J ˆ 9.0, 4H, 4
arom. H(c)), 6.92 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.11 (d, J ˆ 8.1, 4H, 4 arom.
H(c)), 7.14 (d, J ˆ 8.1, 4H, 4 arom. H(c)), 7.22 ± 7.40 (m, 96H, 16 arom.
235 (58), 204 (36), 202 (34), 123 (100), 69 (80), 55 (66), 43 (66); C23H39O2Br
(427.46): calcd C 64.63, H 9.20; found C 64.81, H 9.39.
(Octyl)4 [G2]F COOMe (24): K2CO3 (5.2 g, 37.5 mmol) was added to a
mixture of acetonitrile (100 mL) and acetone (50 mL), and the reaction
mixture was cooled to ice-bath temperature before bromide 23 (8.0 g,
15 mmol, ca. 80% pure), methyl a-resorcylate (1.3 g, 7.5 mmol), and 18-C-6
(0.5 g, 1.9 mmol) were added. After stirring for 20 h at RT the salt was
filtered off and most of the solvent of the filtrate was evaporated. After
addition of CH2Cl2 (50 mL) and H2O (50 mL) and after separation of the
Chem. Eur. J. 1999, 5, No. 11
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0511-3233 $ 17.50+.50/0
3233

D. Seebach and P. B. Rheiner
FULL PAPER
layers, the aqueous layer was extracted (3 Â CH2Cl2). The combined
organic layers were dried over MgSO4 and the solvent evaporated under
vacuum. FC (cyclohexane/CH2Cl2 1:1) yielded 24 (4.7 g, 73%) as a slightly
yellow oil. Rf (cyclohexane/CH2Cl2 1:1): 0.29; 1H NMR (200 MHz): d ˆ
0.8 ± 1.0 (m, 12H, 4 CH3), 1.2 ± 1.5 (m, 40H, 20 CH2), 1.7 ± 1.9 (m, 8H,
4 OCH2CH2), 3.93 (s, 3H, OCH3), 3.96 (t, J ˆ 7.06, 2H, OCH2), 5.01 (s, 2H,
C(arom.)-CH2O), 6.4 (m, 2H, 2 arom. H), 6.6 (m, 4H, 4 arom. H), 6.8 (m,
1H, 1 arom. H), 7.3 (m, 2H, 2 arom. H).
(61), 107 (22); C53H63O6Br (896.13): calcd C 71.04, H 9.34; found C 70.94, H
9.45.
(Octyl)4 [G1]F [G1]*(A) OTBDPS (27): As described in GP III, NaH
(0.24 g, 10 mmol) was added to THF (20 mL). After cooling to ice-bath
temperature a solution of diol 11 (1.12 g, 2.5 mmol) in THF (15 mL) was
added and the reaction mixture was stirred at RT for 1 h, before a solution
of 23 (3.18 g, 7.5 mmol) in THF (15 mL) was added slowly. After stirring at
RT for 3 h the reaction mixture was heated under reflux for 15 h. Workup
as described in GP III yielded a slightly yellow oil as crude product. FC
(CH2Cl2/hexane 1:3) yielded 27 (2.83 g, 99%) as a clear viscous oil. Rf
(Octyl)4 [G2]F OH (25): A solution of ca. 80% of compound 23 (148 g,
346 mmol) in THF (250 mL) was added at ice-bath temperature to a
solution of 3,5-dihydroxybenzylic alcohol (13.0 g, 93 mmol) in THF
(250 mL). Compound 18-C-6 (4.9 g, 18.6 mmol) and K2CO3 (32.1 g,
232 mmol) were added to this solution, and the reaction mixture was
heated under reflux for 30 h. After cooling to RT the salt was filtered off
and most of the solvent of the filtrate was evaporated under vacuum. Et2O
(400 mL) was added to the residue and the solution was washed with H2O
(200 mL). The aqueous layer was extracted (2 Â 600 mL), the combined
organic layers were dried over MgSO4, and the solvent was evaporated
under vacuum to give a brown crude product. FC (CH2Cl2) yielded 25
(42.0 g, 54%) as a slightly yellow oil. A small amount was purified by FC
(CH2Cl2) for analytical purposes. M.p. 38.0 ± 38.18C; Rf (CH2Cl2): 0.28;
1H NMR (400 MHz): d ˆ 0.88 (t, J ˆ 6.9, 12H, 4 CH3), 1.22 ± 1.49 (m, 40H,
20 CH2), 1.65 (t, J ˆ 6.0, 1H, OH), 1.71 ± 1.80 (m, 8H, 4 CH2CH2O), 3.93 (t,
J ˆ 6.6, 8H, 4 CH2O), 4.62 (d, J ˆ 5.8, 2H, CH2OH), 4.95 (s, 4H, 2 benzyl.
CH2), 6.40 (t, J ˆ 2.3, 2H, 2 arom. H), 6.52 ± 6.56 (m, 5H, 5 arom. H), 6.61
(d, J ˆ 2.3, 2H, 2 arom. H); 13C NMR (100 MHz): d ˆ 14.1, 22.7, 26.1, 29.2,
29.3, 29.4, 31.8, 65.4, 68.1, 70.1, 100.8, 101.4, 105.7, 139.0, 143.4, 160.2, 160.5;
IR (CHCl3): nÄ ˆ 3601w, 2928s, 2856m, 1595s, 1456m, 1378w, 1295w, 1166s,
1
(acetone/hexane 1:9): 0.54; H NMR (400 MHz): d ˆ 0.88 (t, J ˆ 6.8, 12H,
4 CH3(P)), 1.09 (s, 9H, tBu), 1.23 (d, J ˆ 6.4, 3H, CH3-C(3)), 1.23 ± 1.48 (m,
40H, 20 CH2(P)), 1.70 ± 1.79 (m, 8H, 4 CH2CH2O(P)), 2.08 ± 2.17 (m, 1H,
H-C(2)), 2.64 (ªddº, ABX, J ˆ 13.5, 8.9, 1H, PhCH2-C(2)), 2.83 (ªddº,
ABX, J ˆ 13.5, 5.8, 1H, PhCH2-C(2)), 3.44 (ªddº, ABX, J ˆ 9.4, 5.7, 1H,
H-C(1)), 3.50 (ªddº, ABX, J ˆ 9.4, 5.1, 1H, H-C(1)), 3.68 ± 3.76 (m, 1H,
H-C(3)), 3.86 ± 3.95 (m, 8H, 4 CH2CH2O(P)), 4.29 ± 4.52 (m, 4H,
2 OCH2Ph(G2)), 4.74 (s, 2H, CH2OSi), 6.34 ± 6.37 (m, 2H, 2 arom.
H(G2)), 6.45 (d, J ˆ 2.3, 2H, 2 arom. H(G2)), 6.50 (d, J ˆ 2.3, 2H, 2 arom.
H(G2)), 7.11 (d, J ˆ 8.1, 2H, 2 arom. H(G1)), 7.23 (d, J ˆ 8.2, 2H, 2 arom.
H(G1)), 7.33 ± 7.44 (m, 6H, 6 arom. H), 7.67 ± 7.72 (m, 4H, 4 arom. H);
13C NMR (100 MHz): d ˆ 14.1, 16.7, 19.3, 22.6, 26.1, 26.8, 29.2, 29.3, 29.4,
31.6, 31.8, 33.1, 46.2, 65.4, 68.0, 69.3, 70.9, 73.0, 74.7, 100.3, 100.4, 105.7,
125.9, 127.7, 129.0, 129.6, 133.6, 135.6, 138.5, 139.7, 141.0, 141.4, 160.3;
‡
MALDI-TOF MS (CCA): m/z: 1136.6, 1164.3 ([M‡Na] ); C74H112O7Si
(1141.78): calcd C 77.84, H 9.89; found C 77.63, H 9.91.
(Octyl)4 [G1]F [G1]*(A) OH (28): As described in GP I, TBAF (2.04 g,
6.46 mmol) was added to a solution of 27 (2.46 g, 2.15 mmol) in THF
(25 mL). Workup as described in GP I yielded a yellow oil (6.7 g). This was
purified by FC (acetone/hexane 1:4) to yield a slightly yellow oil containing
product 28 (2.34 g). A small amount thereof was purified for analytical data
by FC, the rest was used for further reaction steps. Rf (acetone/hexane 1:3):
0.32; 1H NMR (400 MHz): d ˆ 0.88 (t, J ˆ 6.8, 12H, 4 CH3(P)), 1.23 (d, J ˆ
6.3, 3H, CH3-C(3)), 1.23 ± 1.49 (m, 40H, 20 CH2(P)), 1.68 ± 1.80 (m, 8H,
4 CH2CH2O(P)), 2.07 ± 2.18 (m, 1H, H-C(2)), 2.63 (ªddº, ABX, J ˆ 13.5,
8.9, 1H, PhCH2-C(2)), 2.82 (ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-C(2)),
3.38 ± 3.49 (m, 1H, H-C(1)), 3.66 ± 3.73 (m, 1H, H-C(3)), 3.84 ± 3.94 (m, 8H,
4 CH2CH2O(P)), 4.28 ± 4.52 (m, 4H, 2 OCH2Ph(G2)), 4.64 (d, J ˆ 3.2, 2H,
CH2OH), 6.34 ± 6.37 (m, 2H, 2 arom. H(G2)), 6.41 (d, J ˆ 2.3, 2H, 2 arom.
H(G2)), 6.47 (d, J ˆ 2.3, 2H, 2 arom. H(G2)), 7.12 (d, J ˆ 8.1, 2H, 2 arom.
H(G1)), 7.23 (d, J ˆ 8.2, 2H, 2 arom. H(G1)); 13C NMR (100 MHz): d ˆ
14.1, 16.7, 22.7, 26.1, 29.2, 29.3, 29.4, 31.6, 31.8, 33.1, 46.1, 65.3, 68.0, 69.3,
70.9, 73.0, 74.8, 100.3, 100.4, 105.8, 127.7, 129.4, 129.7, 134.8, 140.7, 140.9,
141.3, 160.3.
‡
1058m, 835w cm 1; MS (FAB): m/z: 834 (36.5, [M] ), 833 (50), 832 (26),
816 (13), 696 (14), 695 (49), 694 (100), 693 (35), 692 (36), 58 (11), 467 (13),
457 (11), 349 (11), 348 (32), 347 (38), 163 (12), 149 (11), 137 (19), 125 (57),
124 (33), 123 (30); C53H84O7 (833.23): calcd C 76.40, H 10.16; found C 76.56,
H 9.93.
X-ray crystal structure analysis of 25 (C53H84O7): Determination of the cell
parameters and collection of the reflection intensities were performed on
an Enraf ± Nonius CAD4 four-circle diffractometer (graphite monochro-
mated MoKa radiation, l ˆ 0.7107 Š). Colorless cube, 0.3  0.3  0.5 mm,
triclinic, space group P1, a ˆ 10.578(4) Š, b ˆ 16.045(6) Š, c ˆ 16.688(6) Š,
a ˆ 101.67(3)8, b ˆ 105.96(3)8, g ˆ 100.98(3)8, Vˆ 2574(2) Š3, Z ˆ 2,
1calcd ˆ 1.075 gcm 3, m ˆ 0.069 mm 1, F(000) ˆ 916. Number of reflections
measured 5585 (w scan, 2.6 < 2q < 448, Tˆ 293 K); 5585 unique reflections,
which were used for the determination (direct methods, SHELXS-86).
SHELXL-93 was used for structure refinement (full-matrix least-squares).
The temperature factors of the non-H atoms were refined anisotropically,
the H atoms were added to the molecule with constant isotropic temper-
ature factors on idealized positions and refined according to the riding
model (afix 3). The refinement converged at R ˆ 0.0872 (wR2 ˆ 0.229), min
and max residual electron density 0.438 and 0.215 eŠ 3, number of
variables 541.
(Octyl)4 [G1]F [G1]*(A) Br (29): As described in GP IV, PPh3 (0.79 g,
3 mmol) and CBr4 (1.0 g, 3 mmol) were added to a solution of alcohol 28
(1.94 g, 2.15 mmol) in THF (15 mL). Workup as described in GP IV yielded
a yellow oil (2.86 g). FC (acetone/hexane 1:8) yielded 29 (1.89 g, 91%) as a
1
colorless oil. Rf (acetone/hexane 1:5): 0.56; H NMR (400 MHz): d ˆ 0.88
(t, J ˆ 6.5, 12H, 4 CH3(P)), 1.21 (d, J ˆ 6.4, 3H, CH3-C(3)), 1.22 ± 1.49 (m,
40H, 20 CH2(P)), 1.70 ± 1.80 (m, 8H, 4 CH2CH2O(P)), 2.05 ± 2.13 (m, 1H,
H-C(2)), 2.63 (ªddº, ABX, J ˆ 13.5, 8.8, 1H, PhCH2-C(2)), 2.80 (ªddº,
ABX, J ˆ 13.5, 6.0, 1H, PhCH2-C(2)), 3.39 ± 3.49 (m, 1H, H-C(1)), 3.65 ±
3.72 (m, 1H, H-C(3)), 3.87 ± 3.94 (m, 8H, 4 CH2CH2O(P)), 4.28 ± 4.52 (m,
4H, 2 OCH2Ph(G2)), 4.48 (d, J ˆ 3.2, 2H, CH2Br), 6.34 ± 6.38 (m, 2H, 2
arom. H(G2)), 6.43 (d, J ˆ 2.3, 2H, 2 arom. H(G2)), 6.48 (d, J ˆ 2.3, 2H, 2
arom. H(G2)), 7.09 (d, J ˆ 8.1, 2H, 2 arom. H(G1)), 7.23 (d, J ˆ 8.2, 2H, 2
arom. H(G1)); 13C NMR (100 MHz): d ˆ 14.1, 16.7, 22.6, 26.1, 29.2, 29.3,
29.4, 31.8, 33.2, 33.7, 46.1, 68.0, 69.2, 70.8, 73.1, 74.6, 100.3, 100.4, 105.7,
105.8, 128.9, 129.6, 135.1, 140.8, 141.3, 141.7, 160.0.
(Octyl)4 [G2]F Br (26): As described in GP IV, PPh3 (19.8 g, 76 mmol)
and CBr4 (25.2 g, 76 mmol) were added to a solution of alcohol 25 (42.0 g,
50 mmol) in THF (400 mL). Workup as described in GP IV yielded a
brown crude product. This was stirred in petroleum ether (500 mL) for
15 min and the insoluble parts were filtered off to give, after evaporation of
the solvent, a brownish oil. This was purified of polar by-products by a short
FC (350 g SiO2, CH2Cl2) to yield a yellow oil as 26-containing product
(45.8 g). A small amount was purified again by FC (hexane/Et2O 19:1) for
analytical purposes, the rest was used directly for the next reaction steps. Rf
(CH2Cl2): 0.86; 1H NMR (400 MHz): d ˆ 0.89 (t, J ˆ 6.9, 12H, 4 CH3),
1.22 ± 1.49 (m, 40H, 20 CH2), 1.71 ± 1.81 (m, 8H, 4 CH2CH2O), 3.93 (t, J ˆ
6.6, 8H, 4 CH2O), 4.41 (s, 2H, CH2Br), 4.94 (s, 4H, 2 benzyl. CH2), 6.40 (t,
J ˆ 2.3, 2H, 2 arom. H), 6.52 ± 6.56 (m, 5H, 5 arom. H), 6.62 (d, J ˆ 2.2, 2H,
2 arom. H); 13C NMR (100 MHz): d ˆ 14.1, 22.7, 26.1, 29.2, 29.3, 29.4, 31.8,
33.6, 68.1, 70.2, 100.9, 102.2, 105.8, 108.2, 138.8, 139.8, 160.1, 160.6; IR
(CHCl3): nÄ ˆ 2927s, 2856m, 1595s, 1454m, 1378w, 1296w, 1166s, 1055m,
836w cm 1; MS (FAB): m/z: 896 (21.1), 817 (12), 816 (19), 815 (10), 814
(13), 696 (16), 695 (55), 694 (100), 693 (40), 692 (51), 666 (13), 581 (22), 579
(20), 469 (20), 468 (18), 467 (32), 466 (14), 457 (29), 361 (27), 355 (16), 349
(18), 348 (51), 347 (84), 345 (22), 163 (28), 149 (25), 137 (40), 125 (79), 123
(Octyl)8 [G2]F [G1]*(A) OTBDPS (30): As described in GP III, NaH
(0.55 g, 23 mmol) was added to THF (25 mL). After cooling to ice-bath
temperature, a solution of diol 11 (1.70 g, 3.8 mmol) in THF (25 mL) was
added and the reaction mixture was stirred at RT for 1 h, before a solution
of 26 (8.14 g, 9.1 mmol) in THF (50 mL) was added slowly. After stirring at
RT for 3 h the reaction mixture was heated under reflux for 30 h. Workup
as described in GP III gave a brownish oil (10.2 g) as crude product. FC
(CH2Cl2/hexane 1:2) yielded 30 (6.20 g, 79%) as a clear viscous oil. Rf
(CH2Cl2/hexane 3:2): 0.38; [a]DRT
(400 MHz): d ˆ 0.88 (t, J ˆ 6.8, 24H, 8 CH3(P)), 1.08 (s, 9H, tBu), 1.23 (d,
J ˆ 6.3, 3H, CH3-C(3)), 1.23 ± 1.48 (m, 80H, 40 CH2(P)), 1.68 ± 1.79 (m,
ˆ
1.39 (c ˆ 1.15, CHCl3); 1H NMR
3234
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0511-3234 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 11

Dendritic TADDOLs
3221±3236
16H, 8 CH2CH2O(P)), 2.07 ± 2.14 (m, 1H, H-C(2)), 2.63 (ªddº, ABX, J ˆ
13.5, 9.0, 1H, PhCH2-C(2)), 2.80 (ªddº, ABX, J ˆ 13.5, 5.9, 1H, PhCH2-
C(2)), 3.44 (ªddº, ABX, J ˆ 9.4, 5.6, 1H, H-C(1)), 3.52 (ªddº, ABX, J ˆ 9.4,
4.9, 1H, H-C(1)), 3.66 ± 3.74 (m, 1H, H-C(3)), 3.86 ± 3.94 (m, 16H,
8 CH2CH2O(P)), 4.30 ± 4.53 (m, 4H, 2 OCH2Ph(G2)), 4.73 (s, 2H, CH2O-
Si), 4.90 (d, J ˆ 4.0, 8H, 4 OCH2Ph(G3)), 6.37 ± 6.40 (m, 4H, 4 arom.
H(G3)), 6.48 ± 6.55 (m, 10H, 2 arom. H(G2) and 8 arom. H(G3)), 6.57 (d,
J ˆ 2.3, 2H, 2 arom. H(G2)), 6.60 (d, J ˆ 2.3, 2H, 2 arom. H(G2)), 7.10 (d,
J ˆ 8.1, 2H, 2 arom. H(G1)), 7.22 (d, J ˆ 8.2, 2H, 2 arom. H(G1)), 7.32 ± 7.43
(m, 6H, 6 arom. H), 7.66 ± 7.71 (m, 4H, 4 arom. H); 13C NMR (100 MHz):
d ˆ 14.5, 17.3, 19.7, 23.1, 26.5, 27.3, 29.6, 29.7, 29.8, 32.2, 46.7, 65.8, 68.5, 70.5,
101.2, 101.5, 106.1, 106.7, 106.8, 126.4, 128.1, 129.5, 130.0, 134.0, 136.0, 138.9,
139.5, 140.0, 141.6, 142.0, 160.4, 160.9; IR (CHCl3): nÄ ˆ 3008w, 2929s,
2857m, 1596s, 1455m, 1377w, 1343w, 1295w, 1166s, 1112w, 1047m,
C(2)(c)), 1.22 ± 1.51 (m, 40H, 20 CH2(P)), 1.71 ± 1.83 (m, 8H,
4 CH2CH2O(P)), 3.89 (t, J ˆ 6.6, 4H, 2 CH2O(P)), 3.96 (t, J ˆ 6.6, 4H,
2 CH2O(P)), 4.02 (s, 2H, 2 OH), 4.47 (s, 2H, 2 CH), 6.75 (d, J ˆ 9.0, 4H, 4
arom. H(c)), 6.84 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.21 (d, J ˆ 9.0, 4H, 4 arom.
H(c)), 7.41 (d, J ˆ 9.0, 4H, 4 arom. H(c)); 13C NMR (125 MHz): d ˆ 14.1,
22.6, 26.0, 26.1, 27.2, 29.2, 29.3, 29.4, 31.8, 67.9, 77.6, 81.1, 109.1, 113.0, 113.8,
128.8, 129.7, 134.8, 138.2, 158.2, 158.3; MS (FAB): m/z: 944 (0.7), 493 (13),
451 (9), 441 (8), 440 (36), 439 (100), 437 (17), 436 (13), 435 (36), 424 (15),
423 (47), 327 (13), 311 (10), 233 (33), 211 (16), 199 (19), 121 (77); C63H94O8
(979.43): calcd C 77.26, H 9.67; found C 77.10, H 9.47.
(Octyl)8 {[G1]F}4 [Phe-TADDOL] (34): As described in GP II, a solution
of 23 (1.61 g, 3.77 mmol) in acetone (5 mL) was added to a solution of
TADDOL 2 (0.5 g, 0.94 mmol) in acetone (10 mL). To this solution was
added K2CO3 (0.52 g, 3.77 mmol) and the reaction mixture was heated
under reflux for 30 h. Workup as described in GP II yielded a yellow oil
(2.6 g). FC (acetone/hexane 1:1) yielded 34 (1.73 g, 95%) as a slightly
‡
834w cm 1; MALDI-TOF MS (CCA): m/z: 2074.9, 2102.7 ([M‡Na] ),
‡
2118.6 ([M‡K] ), 2143.3; C134H200O15Si (2079.14): calcd C 77.41, H 9.70;
found C 77.56, H 9.55.
yellow oil. Rf (acetone/hexane 1:2): 0.44; [a]DRT
ˆ
26.0 (c ˆ 1.21, CHCl3);
(Octyl)8 [G2]F [G1]*(A) OH (31): As described in GP I, TBAF (1.20 g,
3.84 mmol) was added to a solution of 30 (4.00 g, 1.92 mmol) in THF
(40 mL). Workup as described in GP I yielded a brownish oil (4.4 g). FC
(Et2O/hexane 1:2) yielded 31 (2.88 g, 81%) as a slightly yellow oil. A small
amount thereof was purified again for analytical data by FC, the rest was
used for further reaction steps. Rf (Et2O/hexane 1:2): 0.18; 1H NMR
(500 MHz): d ˆ 0.88 (t, J ˆ 6.9, 24H, 8 CH3(P)), 1.27 (d, J ˆ 1.8, 3H, CH3-
C(3)), 1.27 ± 1.38 (m, 64H, 32 CH2(P)), 1.38 ± 1.47 (m, 16H,
8 CH2CH2CH2O(P)), 1.69 ± 1.78 (m, 16H, 8 CH2CH2O(P)), 2.06 ± 2.13 (m,
1H, H-C(2)), 2.61 (ªddº, ABX, J ˆ 13.6, 8.8, 1H, PhCH2-C(2)), 2.79 (ªddº,
ABX, J ˆ 13.5, 5.8, 1H, PhCH2-C(2)), 3.42 (ªddº, ABX, J ˆ 9.4, 5.6, 1H,
H-C(1)), 3.47 (ªddº, ABX, J ˆ 9.4, 5.1, 1H, H-C(1)), 3.66 ± 3.72 (m, 1H,
H-C(3)), 3.86 ± 3.94 (m, 16H, 8 CH2CH2O(P)), 4.30 ± 4.52 (m, 4H, 2
OCH2Ph(G2)), 4.61 (d, J ˆ 5.8, 2H, CH2OH), 4.90 (d, J ˆ 6.9, 8H,
4 OCH2Ph(G3)), 6.35 ± 6.40 (m, 4H, 4 arom. H(G3)), 6.49 ± 6.56 (m, 12H,
4 arom. H(G2) and 8 arom. H(G3)), 6.58 (d, J ˆ 2.3, 2H, 2 arom. H(G2)),
7.10 (d, J ˆ 8.1, 2H, 2 arom. H(G1)), 7.22 (d, J ˆ 8.2, 2H, 2 arom. H(G1));
13C NMR (125 MHz): d ˆ 14.1, 16.8, 22.7, 26.1, 29.3, 29.4, 31.8, 46.2, 65.3,
68.1, 69.4, 70.1, 72.9, 74.9, 100.8, 101.1, 105.7, 106.4, 106.5, 127.1, 129.4, 138.4,
139.0, 139.1, 140.6, 141.1, 141.6, 160.0, 160.5; MALDI-TOF MS (CCA):
1H NMR (500 MHz): d ˆ 0.86 ± 0.91 (m, 24H, 8 CH3(P)), 1.05 (s, 6H,
(CH3)2-C(2)(c)), 1.23 ± 1.40 (m, 128H, 64 CH2(P)), 1.40 ± 1.48 (m, 16H,
8 CH2CH2CH2O(P)), 1.72 ± 1.83 (m, 16H, 8 CH2CH2O(P)), 3.88 ± 3.96 (m,
16H, 8 CH2O(P)), 4.49 (s, 2H, 2 CH(c)), 4.93 (s, 4H, 2 PhCH2O(G1)), 4.99
(s, 4H, 2 PhCH2O(G1)), 6.38 (t, J ˆ 2.2, 2H, 2 arom. H(G1)), 6.41 (t, J ˆ
2.2, 2H, 2 arom. H(G1)), 6.52 (s, 4H, 4 arom. H(G1)), 6.58 (s, 2H, 2 arom.
H(G1)), 6.84 (d, J ˆ 9.1, 4H, 4 arom. H(c)), 6.92 (d, J ˆ 9.1, 4H, 4 arom.
H(c)), 7.24 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.43 (d, J ˆ 9.0, 4H, 4 arom. H(c));
13C NMR (125 MHz): d ˆ 14.1, 22.7, 26.1, 27.2, 29.2, 29.3, 29.4, 31.8, 68.1,
70.0, 77.6, 81.1, 100.8, 100.9, 105.7, 105.8, 109.2, 113.5, 114.3, 128.9, 129.7,
135.3, 138.7, 139.2, 157.9, 158.0, 160.5; IR (CHCl3): nÄ ˆ 3364w, 2933s, 2872s,
1718w, 1600s, 1508m, 1456s, 1380m, 1297m, 1169s, 1107s, 1062s, 907m,
1
‡
836m cm
;
MALDI-TOF MS (CCA): m/z: 1940.2 ([M‡Na] );
C123H182O16 (1916.78): calcd C 77.07, H 9.57; found C 77.11, H 9.40.
(Octyl)16 {[G2]F}4 [Phe-TADDOL] (35): As described in GP II, a solution
of 26 (2.95 g, 3.3 mmol) in acetone (20 mL) was added to a solution of
TADDOL 2 (0.4 g, 0.75 mmol) in acetone (20 mL). To this solution was
added K2CO3 (0.42 g, 3 mmol) and the reaction mixture was heated under
reflux for 30 h. Workup as described in GP II yielded a yellow oil (2.46 g).
FC (acetone/hexane 1:19) yielded 35 (0.80 g, 28%) as a colorless oil. Rf
‡
‡
m/z: 1836.0, 1864.2 ([M‡Na] ), 1879.9 ([M‡K] ), 1904.3; C118H182O15
(acetone/hexane 1:2): 0.61; [a]DRT
ˆ
16.4 (c ˆ 1.21, CHCl3); 1H NMR
(1840.73): calcd C 77.00, H 9.97; found C 77.02, H 10.04.
(400 MHz): d ˆ 0.66 ± 0.82 (m, 48H, 16 CH3(P)), 1.06 (s, 6H, (CH3)2-
C(2)(c)), 1.24 ± 1.48 (m, 320H, 160 CH2(P)), 1.40 ± 1.65 (m, 32H,
16 CH2CH2O(P)), 3.77 ± 3.96 (m, 32H, 16 CH2O(P)), 4.46 (s, 2H,
2 CH(c)), 4.80 ± 4.96 (m, 8H, 4 PhCH2O(G1)), 6.35 ± 6.41 (m, 12H, 4 arom.
H(G1) and 8 arom. H(G2)), 6.55 ± 6.59 (m, 20H, 4 arom. H(G1) and 16
arom. H(G2)), 6.81 (d, J ˆ 8.2, 4H, 4 arom. H(c)), 6.93 (d, J ˆ 8.2, 4H, 4
arom. H(c)), 7.23 (d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.46 (d, J ˆ 9.0, 4H, 4 arom.
H(c)); 13C NMR (125 MHz): d ˆ 14.1, 22.7, 26.1, 27.2, 29.2, 29.4, 30.9, 31.8,
68.1, 70.2, 100.9, 105.7, 105.8, 128.9, 129.8, 138.9, 160.1, 160.2, 160.5; IR
(CHCl3): nÄ ˆ 2928s, 2857m, 1596s, 1508w, 1456m, 1372m, 1296m, 1167s,
1057m, 836w cm 1; MALDI-TOF MS (HABA): m/z: 3346.8, 3580.3,
(Octyl)8 [G2]F [G1]*(A) Br (32): As described in GP IV, PPh3 (0.56 g,
2.12 mmol) and CBr4 (0.7 g, 2.12 mmol) were added to a solution of alcohol
31 (2.60 g, 1.41 mmol) in THF (15 mL). Workup as described in GP IV
yielded a yellow oil (4.02 g). FC (CH2Cl2/hexane 8:1) yielded 32 (1.13 g,
42%) as a colorless oil. Rf (CH2Cl2/hexane 8:1): 0.74; 1H NMR (500 MHz):
d ˆ 0.88 (t, J ˆ 6.9, 24H, 8 CH3(P)), 1.21 (d, J ˆ 6.3, 3H, CH3-C(3)), 1.27 ±
1.38 (m, 64H, 32 CH2(P)), 1.38 ± 1.46 (m, 16H, 8 CH2CH2CH2O(P)), 1.71 ±
1.77 (m, 16H, 8 CH2CH2O(P)), 2.04 ± 2.09 (m, 1H, H-C(2)), 2.61 (ªddº,
ABX, J ˆ 13.6, 8.7, 1H, PhCH2-C(2)), 2.77 (ªddº, ABX, J ˆ 13.5, 5.9, 1H,
PhCH2-C(2)), 3.42 (ªddº, ABX, J ˆ 9.4, 4.0, 1H, H-C(1)), 3.47 (ªddº, ABX,
J ˆ 9.4, 5.0, 1H, H-C(1)), 3.64 ± 3.69 (m, 1H, H-C(3)), 3.88 ± 3.98 (m, 16H,
8 CH2CH2O(P)), 4.30 ± 4.51 (m, 6H, 2 OCH2Ph(G2) and CH2Br), 4.90 (d,
J ˆ 6.9, 8H, 4 OCH2Ph(G3)), 6.37 ± 6.39 (m, 4H, 4 arom. H(G3)), 6.50 ±
6.56 (m, 4H, 4 arom. H(G2) and 8 arom. H(G3)), 6.58 (d, J ˆ 2.3, 2H, 2
arom. H(G2)), 7.07 (d, J ˆ 8.2, 2H, 2 arom. H(G1)), 7.24 (d, J ˆ 8.2, 2H, 2
arom. H(G1)); 13C NMR (125 MHz): d ˆ 14.1, 16.8, 22.7, 26.1, 29.3, 29.4,
31.8, 33.3, 33.7, 46.2, 68.1, 69.3, 70.1, 70.8, 73.0, 74.7, 100.8, 101.1, 105.7, 106.4,
106.5, 127.7, 129.0, 129.6, 135.2, 139.1, 140.6, 141.1, 141.5, 141.6, 160.0, 160.5;
‡
3814.9 ([M‡Na] ); C243H358O32 (3791.48): calcd C 76.98, H 9.52; found C
76.96, H 9.37.
(Octyl)32 {[G2]F [G1]*(A)}4 [Phe-TADDOL] (36): As described in
GP II, a solution of 32 (1.21 g, 0.636 mmol) in acetone (10 mL) was added
to a solution of TADDOL 2 (76.6 mg, 0.145 mmol) in acetone (30 mL). To
this solution was added K2CO3 (0.1 g, 0.722 mmol), and the reaction
mixture was heated under reflux for 110 h. Workup as described in GP II
yielded a brownish oil (0.70 g) as crude product. Three FC runs (acetone/
hexane 1:4, acetone/hexane 1:99, hexane) yielded 36 (54 mg, 5%) as a
colorless oil (the difficulty in identification of the product led to a big loss of
product after the first column chromatographies). Rf (acetone/hexane 1:3):
0.75; 1H NMR (500 MHz): d ˆ 0.85 ± 0.88 (m, 96H, 32 CH3(P)), 1.07 (s, 6H,
(CH3)2-C(2)(c)), 1.20 ± 1.38 (m, 259H, 128 CH2(P) and CH3-C(3)), 1.38 ±
‡
MALDI-TOF MS (HABA): m/z: 1846.8, 1927.9 ([M‡Na] ), 2102.8;
C118H181O14Br (1903.62): calcd C 74.45, H 9.58; found C 75.10, H 9.52.
(Octyl)4 {[G0]}4 [Phe-TADDOL] (33): n-Octyl bromide (1.45 g,
7.53 mmol) was added to a solution of TADDOL 2 (1.00 g, 1.88 mmol) in
DMF (5 mL). To this solution was added previously dried, finely powdered
K2CO3 (1.04 g, 7.53 mmol), and the resulting suspension was heated under
reflux for 2 h. After cooling to RT, H2O (30 mL) and CH2Cl2 (100 mL) were
added, and the solids were filtered off and rinsed with CH2Cl2. The two
layers of the filtrate were separated; the aqueous layer was extracted (2 Â
Et2O). The combined organic layers were washed with H2O. The combined
organic layers were dried over MgSO4 and the solvent was evaporated to
yield a yellow oil (1.70 g). FC (acetone/hexane 1:19) yielded 33 (0.477 g,
26%) as a clear viscous oil. Rf (acetone/hexane 1:2): 0.44; 1H NMR
(400 MHz): d ˆ 0.85 ± 0.91 (m, 12H, 4 CH3(P)), 1.06 (s, 6H, (CH3)2-
1.46
(m,
64H,
32 CH2CH2CH2O(P)),
1.70 ± 1.75
(m,
64H,
32 CH2CH2O(P)), 2.06 ± 2.13 (m, 1H, H-C(2)), 2.62 ± 2.67 (m, 1H,
PhCH2-C(2)), 2.76 ± 2.83 (m, 1H, PhCH2-C(2)), 3.42 ± 3.46 (m, 1H,
H-C(1)), 3.46 ± 3.53 (m, 1H, H-C(1)), 3.67 ± 3.72 (m, 1H, H-C(3)), 3.87 ±
3.91 (m, 64H, 32 CH2CH2O(P)), 4.30 ± 4.53 (m, 24H, 8 OCH2Ph(G2) and
4 OCH2Ph(G1)), 4.87 ± 5.00 (m, 32H, 16 OCH2Ph(G3)), 6.36 ± 6.38 (m, 16
arom. H(G3)), 6.49 ± 6.56 (m, 48H, 16 arom. H(G2) and 32 arom. H(G3)),
6.58 ± 6.59 (m, 8H, 8 arom. H(G2)), 6.83 (d, J ˆ 8.7, 4H, 4 arom. H(c)), 6.92
(d, J ˆ 9.0, 4H, 4 arom. H(c)), 7.13 ± 7.18 (m, 8H, 8 arom. H(G1)), 7.22 ± 7.28
Chem. Eur. J. 1999, 5, No. 11
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0511-3235 $ 17.50+.50/0
3235

D. Seebach and P. B. Rheiner
FULL PAPER
(m, 8H, 8 arom. H(G1)), 7.31 ± 7.46 (2d, J ˆ 8.7, 8H, 8 arom. H(c));
13C NMR (125 MHz): d ˆ 14.1, 16.9, 19.0, 22.7, 26.1, 29.2, 29.3, 29.4, 31.8,
68.1, 69.3, 69.9, 70.1, 70.8, 73.0, 74.8, 100.8, 101.1, 105.7, 106.3, 106.4, 127.7,
128.9, 129.4, 129.7, 134.8, 135.2, 139.1, 141.1, 141.6, 160.0, 160.5.
[17] G. R. Newkome, Z.-Q. Yao, G. R. Baker, V. K. Gupta, J. Org. Chem.
1985, 50, 2003.
[18] S. Stevelmans, J. C. M. van Hest, J. F. G. A. Jansen, D. A. F. J. van -
Boxtel, E. M. M. de Brabander-van den Berg, E. W. Meijer, J. Am.
Chem. Soc. 1996, 118, 7398.
[19] The same type of branches of up to the third generation have been
independently prepared by another group: Z. Bo, X. Zhang, X. Yi, M.
Yang, J. Shen, Y. Rehn, S. Xi, Polymer Bulletin 1997, 38, 257.
[20] D. Seebach, A. K. Beck, B. Schmidt, Y. M. Wang, Tetrahedron 1994,
50, 4363.
[21] A. K. Beck, B. Bastani, D. A. Plattner, W. Petter, D. Seebach, H.
Braunschweiger, P. Gysi, L. LaVecchia, Chimia 1991, 45, 238.
[22] D. C. Reiber, R. S. Brown, S. Weinberger, J. Kenny, J. Bailey, Anal.
Chem. 1998, 70, 1214.
The general procedure for carrying out TADDOL-catalyzed Et2Zn
additions to PhCHO has been previously published.[13]
Acknowledgments
We gratefully acknowledge the financial support of the Swiss National
Science Foundation (project no. 2100-040659.94 and CHiral2, project no.
20-48157.96). We also thank Dr. T. Butz and P. Eisenring for the preparation
of some compounds employed in the work described. The following
companies provided chemicals: Hüls, Troisdorf (titanates), Schering,
Bergkamen (Et2Zn), Chemische Fabrik Uetikon, Uetikon (diethyl tar-
trate). Continuing generous fincancial support by Novartis (Basel) is
gratefully acknowledged.
[23] D. Seebach, J.-M. Lapierre, G. Greiveldinger, K. Skobridis, Helv.
Chim. Acta 1994, 77, 1673.
[24] For an investigation of the influence of chiral building blocks on the
optical activity of dendritic poly(benzyl ether) branches, see: D. M.
Junge, D. V. McGrath, Polym. Mater. Sci. Eng. 1997, 77, 154.
[25] Using (achiral) dendritic bis(oxazoline) ± CuII complexes to catalyze
Diels ± Alder reactions, Chow et al. also found a big difference in
activity when going from the second to the third generation: H.-F.
Chow, C. C. Mak, J. Org. Chem. 1997, 62, 5116.
[26] D. Seebach, J.-M. Lapierre, W. Jaworek, P. Seiler, Helv. Chim. Acta
1993, 76, 459; J.-M. Lapierre, K. Skobridis, D. Seebach, Helv. Chim.
Acta 1993, 76, 2419.
[27] D. Seebach, A. K. Beck, R. Breitschuh, K. Job, Org. Synth. 1992, 71,
39.
[28] J. Ehrler, F. Giovanni, B. Lamatsch, D. Seebach, Chimia 1986, 40, 172.
[29] B. Bachmann, D. Seebach, Helv. Chim. Acta 1998, 81, 2430.
[30] The amounts of the previously mentioned by-products resulting from
fivefold coupling were not determined.
[1] For a recent review on chiral dendritic catalysts and chiral dendrimers,
see: D. Seebach, P. B. Rheiner, G. Greiveldinger, T. Butz, H. Sellner,
Top. Curr. Chem. 1998, 197, 125.
[2] H. W. I. Peerlings, E. W. Meijer, Chem. Eur. J. 1997, 3, 1563;
M. S. T. H. Sanders-Hovens, J. F. G. A. Jansen, J. A. J. M. Vekemans,
E. W. Meijer, Polym. Mater. Sci. Eng. 1995, 73, 338.
[3] D. Seebach, R. E. Marti, T. Hintermann, Helv. Chim. Acta 1996, 79,
1710.
[4] T. Suzuki, Y. Hirokawa, K. Ohtake, T. Shibata, K. Soai, Tetrahedron
Asymmetry 1997, 8, 4033.
[5] D. A. Tomalia, P. R. Dvornic, Nature 1994, 372, 617.
[31] H. B. Bürgi, J. D. Dunitz, in Structure Correlation, Vols. 1 and 2, VCH,
Weinheim, 1994.
[6] H. Brunner, J. Fürst, Tetrahedron 1994, 50, 4303; H. Brunner, S.
Altmann, Chem. Ber. 1994, 127, 2285.
[32] S. N. Vinogradov, R. H. Linnell, in Hydrogen Bonding, Van Nostrand
Reinhold, New York, 1987, p. 176.
[7] In ref. [2], Meijer et al. describe the catalysis with different gener-
ations of poly(propylene imine) dendrimers which carry chiral amino
alcohol moieties on their periphery. Due to interactions between the
amino alcohol moieties and due to crowding on the surface of the
dendrimers, the selectivities of these catalysts decrease with increasing
size of the catalyst. Even though interactions within the catalyst
molecules could be decreased by use of a different amino alcohol, the
crowding effect still prevented good reaction selectivities.
[8] J. F. G. A. Jansen, E. M. M. de Brabander-van den Berg, E. W. Meijer,
Science 1994, 266, 1226; J. F. G. A. Jansen, H. W. I. Peerlings, E. M. M.
de Brabander-van den Berg, E. W. Meijer, Angew. Chem. 1995, 107,
1321; Angew. Chem. Int. Ed. Engl. 1995, 34, 1206. With their work on
dendritic boxes, Meijer et al. demonstrate a selective inclusion of
organic molecules inside a poly(propylene imine) dendrimer with the
densely packed surface groups preventing the release of the mole-
cules.
[33] The X-ray structure of a similar second-generation branch with
benzylic groups at the periphery has been described previously and
shows a planar array of the molecules: B. Karakaya, W. Claussen, K.
Gessler, W. Saenger, A.-D. Schlüter, J. Am. Chem. Soc. 1997, 119,
3296.
[34] P. K. Murer, J.-M. Lapierre, G. Greiveldinger, D. Seebach, Helv. Chim.
Acta 1997, 80, 1648. For the interpretation of the 1H NMR spectra the
following abbreviations were used: c for core, Gx for generation
number x, P for periphery. The TADDOL core and the branching
units were described and numbered as shown.
O
O
3
1
4
5
O
O
[9] In ref. [4], Soai et al. describe the catalysis with ephedrine derivatives
attached to poly(amido amine) dendrimers. The selectivity of the
catalyzed reaction decreases rapidly with increasing size of the
dendrimer used (even in lower generations). The authors explain this
effect with interactions between the ephedrine units. It is, however,
also possible that the loss of selectivity results from interactions with
the polar dendritic branches.
O
2
OH
OH
O
O
O
[G1]F
[10] In ref. [6], Brunner et al. describe very poor selectivities of reactions
catalyzed by achiral catalytic sites with chiral dendritic branches. To
the best of our knowledge, no other work has yet been published on
the influence of dendritic branches on a catalytically active core.
[11] For short review articles, see: R. Dahinden, A. K. Beck, D. Seebach, in
Encyclopedia of Reagents for Organic Synthesis, Vol. 3 (Ed.: L.
Paquette), Wiley, Chichester, 1995, p. 2167.
[Phe-TADDOL]
O
1
O
1
2
2
3
O
3
O
[12] For a first preliminary account see: P. B. Rheiner, H. Sellner, D.
Seebach, Helv. Chim. Acta 1997, 80, 2027; P. B. Rheiner, D. Seebach,
Polym. Mater. Sci. Eng. 1997, 77, 130.
[13] D. Seebach, D. A. Plattner, A. K. Beck, Y. M. Wang, D. Hunziker, W.
Petter, Helv. Chim. Acta 1992, 75, 2171.
[14] For a dendrimer with peripheral TADDOL units, see ref. [3].
[G1]*(A)
[G1]*(B)
[35] D. Seebach, J. Zimmermann, Helv. Chim. Acta 1986, 69, 1147.
Â
[15] C. J. Hawker, J. M. J. Frechet, J. Am. Chem. Soc. 1990, 112, 7638.
Received: March 24, 1999 [F1695]
[16] P. Murer, D. Seebach, Helv. Chim. Acta 1998, 81, 603.
3236
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Chem. Eur. J. 1999, 5, No. 11